Cd19

Summary

Gene Symbol: Cd19
Description: CD19 antigen
Alias: AW495831, B-lymphocyte antigen CD19, differentiation antigen CD19
Species: mouse

Top Publications

  1. ncbi CD19 is essential for B cell activation by promoting B cell receptor-antigen microcluster formation in response to membrane-bound ligand
    David Depoil
    Lymphocyte Interaction Laboratory, London Research Institute, Cancer Research UK, 44 Lincoln s Inn Fields, London WC2A 3PX, UK
    Nat Immunol 9:63-72. 2008
  2. doi Phosphoinositide 3-kinase activity in T cells regulates the magnitude of the germinal center reaction
    Julia Rolf
    Laboratory of Lymphocyte Signalling and Development, Babraham Institute, Cambridge, United Kingdom
    J Immunol 185:4042-52. 2010
  3. ncbi TGF-beta receptor controls B cell responsiveness and induction of IgA in vivo
    B B Cazac
    Department of Medicine, The Windeyer Institute of Medical Sciences, University College, London, United Kingdom
    Immunity 13:443-51. 2000
  4. pmc Follicular shuttling of marginal zone B cells facilitates antigen transport
    Guy Cinamon
    Howard Hughes Medical Institute and Department of Microbiology and Immunology, University of California, San Francisco, California 94143, USA
    Nat Immunol 9:54-62. 2008
  5. pmc Tumor necrosis factor receptor-associated factor 3 is a critical regulator of B cell homeostasis in secondary lymphoid organs
    Ping Xie
    Department of Microbiology, The University of Iowa, Iowa City, IA 52242, USA
    Immunity 27:253-67. 2007
  6. ncbi Abnormal B lymphocyte development, activation, and differentiation in mice that lack or overexpress the CD19 signal transduction molecule
    P Engel
    Department of Immunology, Duke University Medical Center, Durham, North Carolina 27710, USA
    Immunity 3:39-50. 1995
  7. pmc Enhanced Toll-like receptor (TLR) responses of TNFR-associated factor 3 (TRAF3)-deficient B lymphocytes
    Ping Xie
    Department of Microbiology, The University of Iowa, Iowa City, Iowa, USA
    J Leukoc Biol 90:1149-57. 2011
  8. pmc IFN regulatory factor 8 restricts the size of the marginal zone and follicular B cell pools
    Jianxun Feng
    Laboratory of Immunopathology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA
    J Immunol 186:1458-66. 2011
  9. ncbi Regulation of class-switch recombination and plasma cell differentiation by phosphatidylinositol 3-kinase signaling
    Sidne A Omori
    Program of Inflammatory Disease Research, Infectious and Inflammatory Disease Center and Program of Signal Transduction, Cancer Center, Burnham Institute for Medical Research, La Jolla, California 92037, USA
    Immunity 25:545-57. 2006
  10. ncbi Impairment of T-cell-dependent B-cell responses and B-1 cell development in CD19-deficient mice
    R C Rickert
    Institute for Genetics, University of Cologne, Germany
    Nature 376:352-5. 1995

Research Grants

  1. Effect of Antibodies/Chemotherapy on Childhood Leukemia
    LARRY HERRERA; Fiscal Year: 2007
  2. Regulation of T cell activation and tolerance by Grail
    ROZA INSAFETDINOVNA NURIEVA; Fiscal Year: 2010

Scientific Experts

Detail Information

Publications111 found, 100 shown here

  1. ncbi CD19 is essential for B cell activation by promoting B cell receptor-antigen microcluster formation in response to membrane-bound ligand
    David Depoil
    Lymphocyte Interaction Laboratory, London Research Institute, Cancer Research UK, 44 Lincoln s Inn Fields, London WC2A 3PX, UK
    Nat Immunol 9:63-72. 2008
    ..containing immunoglobulin (Ig) M and IgD that recruit the kinase Syk and transiently associate with the coreceptor CD19. Unexpectedly, CD19-deficient B cells were significantly defective in initiation of BCR-dependent signaling, ..
  2. doi Phosphoinositide 3-kinase activity in T cells regulates the magnitude of the germinal center reaction
    Julia Rolf
    Laboratory of Lymphocyte Signalling and Development, Babraham Institute, Cambridge, United Kingdom
    J Immunol 185:4042-52. 2010
    ..Our findings support a model in which the magnitude of the GC reaction is controlled by the activity of the PI3K pathway in T(FH) cells...
  3. ncbi TGF-beta receptor controls B cell responsiveness and induction of IgA in vivo
    B B Cazac
    Department of Medicine, The Windeyer Institute of Medical Sciences, University College, London, United Kingdom
    Immunity 13:443-51. 2000
    ..The data reveal differential roles of TbetaR in homeostasis and antigen responsiveness of B cell subpopulations and establish a critical function of the TGF-beta receptor ligand pair in the induction of IgA responses in vivo...
  4. pmc Follicular shuttling of marginal zone B cells facilitates antigen transport
    Guy Cinamon
    Howard Hughes Medical Institute and Department of Microbiology and Immunology, University of California, San Francisco, California 94143, USA
    Nat Immunol 9:54-62. 2008
    ..Marginal zone-follicle shuttling of marginal zone B cells provides an efficient mechanism for systemic antigen capture and delivery to follicular dendritic cells...
  5. pmc Tumor necrosis factor receptor-associated factor 3 is a critical regulator of B cell homeostasis in secondary lymphoid organs
    Ping Xie
    Department of Microbiology, The University of Iowa, Iowa City, IA 52242, USA
    Immunity 27:253-67. 2007
    ..These findings indicate that TRAF3 is a critical regulator of peripheral B cell homeostasis and may be implicated in the regulation of peripheral self-tolerance induction...
  6. ncbi Abnormal B lymphocyte development, activation, and differentiation in mice that lack or overexpress the CD19 signal transduction molecule
    P Engel
    Department of Immunology, Duke University Medical Center, Durham, North Carolina 27710, USA
    Immunity 3:39-50. 1995
    b>CD19-deficient mice were generated to examine the role of CD19 in B cell growth regulation in vivo...
  7. pmc Enhanced Toll-like receptor (TLR) responses of TNFR-associated factor 3 (TRAF3)-deficient B lymphocytes
    Ping Xie
    Department of Microbiology, The University of Iowa, Iowa City, Iowa, USA
    J Leukoc Biol 90:1149-57. 2011
    ..Additionally, TRAF3(-/-) B cells displayed enhanced TLR-mediated expression of AID and Ig isotype switching. Thus, TRAF3 plays varied and cell type-specific, biological roles in TLR responses...
  8. pmc IFN regulatory factor 8 restricts the size of the marginal zone and follicular B cell pools
    Jianxun Feng
    Laboratory of Immunopathology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA
    J Immunol 186:1458-66. 2011
    ..the B cell-intrinsic effects of IRF8 deficiency, we generated mice with a conditional allele of Irf8 crossed with CD19-Cre mice (designated IRF8-conditional knockout [CKO])...
  9. ncbi Regulation of class-switch recombination and plasma cell differentiation by phosphatidylinositol 3-kinase signaling
    Sidne A Omori
    Program of Inflammatory Disease Research, Infectious and Inflammatory Disease Center and Program of Signal Transduction, Cancer Center, Burnham Institute for Medical Research, La Jolla, California 92037, USA
    Immunity 25:545-57. 2006
    ..However, ectopic expression of AID could not fully overcome inhibition of CSR by PI3K, suggesting that PI3K regulates both the expression and function of AID...
  10. ncbi Impairment of T-cell-dependent B-cell responses and B-1 cell development in CD19-deficient mice
    R C Rickert
    Institute for Genetics, University of Cologne, Germany
    Nature 376:352-5. 1995
    b>CD19 is the hallmark differentiation antigen of the B lineage...
  11. pmc B lymphocyte-specific, Cre-mediated mutagenesis in mice
    R C Rickert
    Institute for Genetics, University of Cologne, Weyertal 121, 50931 Cologne, Germany
    Nucleic Acids Res 25:1317-8. 1997
    ..To selectively modify genes in B lymphocytes, we have generated mice (designated CD19-Cre) which express cre under the transcriptional control of the B lineage-restricted CD19 gene...
  12. ncbi Role of CXCR5 and CCR7 in follicular Th cell positioning and appearance of a programmed cell death gene-1high germinal center-associated subpopulation
    Nicole M Haynes
    Howard Hughes Medical Institute, University of California, San Francisco, CA 94143, USA
    J Immunol 179:5099-108. 2007
    ....
  13. ncbi The PI3K p110delta is required for down-regulation of RAG expression in immature B cells
    Miriam Llorian
    Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Cambridge, United Kingdom
    J Immunol 178:1981-5. 2007
    ..These results demonstrate a role for p110delta in the regulation of RAG gene expression and thereby LC allelic/isotype exclusion...
  14. pmc In vivo regulation of Bcl6 and T follicular helper cell development
    Amanda C Poholek
    Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06520, USA
    J Immunol 185:313-26. 2010
    ..These data increase our understanding of Bcl6 regulation in T(FH) cells and their differentiation in vivo and identifies a new surface marker that may be functionally relevant in this subset...
  15. ncbi Cellular niches controlling B lymphocyte behavior within bone marrow during development
    Koji Tokoyoda
    Department of Medical Systems Control, Institute for Frontier Medical Sciences, Kyoto University, 53 Kawahara cho, Shogoin, Sakyo ku, Kyoto 606 8507, Japan
    Immunity 20:707-18. 2004
    ..Plasma cells again seed CXCL12-expressing cells. We demonstrate the B lymphocyte characteristic location and movement between specific niches within bone marrow during development and suggest that CXCL12 maintains the cells in the niche...
  16. ncbi BCAP: the tyrosine kinase substrate that connects B cell receptor to phosphoinositide 3-kinase activation
    T Okada
    Department of Molecular Genetics, Institute for Liver Research, Kansai Medical University, Moriguchi, Japan
    Immunity 13:817-27. 2000
    ..Hence, these data suggest that BCAP bridges BCR-associated kinases to the PI3K pathway by regulating PI3K localization...
  17. ncbi Altered splenic B cell subset development in mice lacking phosphoinositide 3-kinase p85alpha
    Amber C Donahue
    Center for Immunology and Department of Molecular Biology and Biochemistry, University of California, Irvine, CA, USA
    Int Immunol 16:1789-98. 2004
    ..These findings establish a role for PI3K-p85alpha in differentiation of both follicular and marginal zone B cells, and suggest that these functions are required not solely for the propagation of anti-apoptotic signals...
  18. ncbi The effect of deleting p110delta on the phenotype and function of PTEN-deficient B cells
    Michelle L Janas
    Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Babraham, Cambridge, United Kingdom
    J Immunol 180:739-46. 2008
    ..These results demonstrate an epistatic relationship between p110delta and PTEN. In addition, they also suggest that additional PI3K catalytic subunits contribute to B cell development and function...
  19. ncbi Regulation of B-cell development by BCAP and CD19 through their binding to phosphoinositide 3-kinase
    Yuichi Aiba
    Laboratory for Lymphocyte Differentiation, RIKEN Research Center for Allergy and Immunology, Tsurumi ku, Yokohama, Japan
    Blood 111:1497-503. 2008
    ..In this study, we show that deletion of both BCAP and CD19 leads to an almost complete block of BCR-mediated Akt activation and to severe defects in generation of immature ..
  20. ncbi Isolation of cDNAs encoding the CD19 antigen of human and mouse B lymphocytes. A new member of the immunoglobulin superfamily
    T F Tedder
    Division of Tumor Immunology, Dana Farber Cancer Institute, Boston, MA 02115
    J Immunol 143:712-7. 1989
    The CD19 (B4) molecule is a m.w. 95,000 cell-surface protein of human B lymphocytes that is expressed before Ig and persists throughout differentiation...
  21. pmc XBP1 governs late events in plasma cell differentiation and is not required for antigen-specific memory B cell development
    Derrick J Todd
    Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA
    J Exp Med 206:2151-9. 2009
    ..We have developed an XBP1(fl/fl) CD19(+/cre) conditional knockout (XBP1(CD19)) mouse to build upon our current understanding of the function of XBP1 in ..
  22. ncbi E2A proteins are required for proper B cell development and initiation of immunoglobulin gene rearrangements
    G Bain
    Department of Biology, University of California, San Diego, La Jolla 92130
    Cell 79:885-92. 1994
    ..While immunoglobulin germline I mu RAG-1, mb-1, CD19, and lambda 5 transcripts are dramatically reduced in fetal livers of E2A (-/-) mice, B29 and mu degrees ..
  23. ncbi B4, a human B lymphocyte-associated antigen expressed on normal, mitogen-activated, and malignant B lymphocytes
    L M Nadler
    J Immunol 131:244-50. 1983
    ..Moreover, the observation that B4 is expressed on almost all early B cell tumors suggests that it may precede B1, CALLA, cytoplasmic mu, and B2 in early B cell ontogeny...
  24. ncbi The calcineurin phosphatase complex modulates immunogenic B cell responses
    Monte M Winslow
    Program in Immunology, Stanford University, Stanford, California 94305, USA
    Immunity 24:141-52. 2006
    ..By several different criteria, calcineurin is dispensable for B cell tolerance, indicating that this phosphatase complex modulates immunogenic, but not tolerogenic, responses in vivo...
  25. pmc Suppression of phosphatidylinositol 3,4,5-trisphosphate production is a key determinant of B cell anergy
    Cecille D Browne
    Program of Inflammatory Disease Research, Infectious and Inflammatory Disease Center and Program of Signal Transduction, Cancer Center, Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
    Immunity 31:749-60. 2009
    ..of PI(3,4,5)P(3) in anergic B cells, which was attributable to reduced phosphorylation of the PI3K membrane adaptor CD19, as well as increased expression of the inositol phosphatase PTEN...
  26. pmc B-lymphoid cells with attributes of dendritic cells regulate T cells via indoleamine 2,3-dioxygenase
    Burles A Johnson
    Immunotherapy and Cancer Centers, Departments of Pathology and Medicine, and Flow Cytometry Core Facility, Medical College of Georgia, Augusta, GA 30912, USA
    Proc Natl Acad Sci U S A 107:10644-8. 2010
    A discrete population of splenocytes with attributes of dendritic cells (DCs) and coexpressing the B-cell marker CD19 is uniquely competent to express the T-cell regulatory enzyme indoleamine 2,3-dioxygenase (IDO) in mice treated with ..
  27. ncbi B-1a and B-1b cells exhibit distinct developmental requirements and have unique functional roles in innate and adaptive immunity to S. pneumoniae
    Karen M Haas
    Department of Immunology, Box 3010, Duke University Medical Center, Durham, North Carolina 27710, USA
    Immunity 23:7-18. 2005
    ..Transgenic mice overexpressing CD19 (hCD19Tg) generated B-1a cells and natural antibodies that provided protection during infection, while CD19-..
  28. pmc BTB-ZF factors recruit the E3 ligase cullin 3 to regulate lymphoid effector programs
    Rebecca Mathew
    Committee on Immunology, Department of Pathology, The Howard Hughes Medical Institute, University of Chicago, Chicago, Illinois 60637, USA
    Nature 491:618-21. 2012
    ..We propose that this new function is essential to direct the differentiation of several T- and B-cell effector programs, and may also be involved in the oncogenic role of PLZF and BCL6 in leukaemias and lymphomas...
  29. ncbi BCR signal through alpha 4 is involved in S6 kinase activation and required for B cell maturation including isotype switching and V region somatic hypermutation
    Seiji Inui
    Department of Immunology, Kumamoto University School of Medicine, 2 2 1 Honjo, Kumamoto 860 0811, Japan
    Int Immunol 14:177-87. 2002
    ..role for alpha 4 in B cell activation, the alpha 4 gene was disrupted conditionally in B cells by mating male CD19-Cre mice with female alpha 4-floxed mice...
  30. ncbi Canonical NF-kappaB activity, dispensable for B cell development, replaces BAFF-receptor signals and promotes B cell proliferation upon activation
    Yoshiteru Sasaki
    The CBR Institute for Biomedical Research, Harvard Medical School, 200 Longwood Avenue, Boston, Massachusetts 02115, USA
    Immunity 24:729-39. 2006
    ..differentiation and proper localization of follicular and marginal zone B cells in the absence of BAFF-R, but not CD19. By replacing BAFF-R signals, constitutive canonical NF-kappaB signaling, a hallmark of various B cell lymphomas, ..
  31. pmc MicroRNAs prevent the generation of autoreactive antibodies
    Laura Belver
    DNA Hypermutation and Cancer Group, Spanish National Cancer Research Center CNIO, Madrid 28029, Spain
    Immunity 33:713-22. 2010
    ..Here, we have examined the role of microRNAs in terminal B cell differentiation by analyzing Cd19-Cre(ki/+) Dicer1(fl/fl) mice...
  32. ncbi Gene repression by Pax5 in B cells is essential for blood cell homeostasis and is reversed in plasma cells
    Alessio Delogu
    Research Institute of Molecular Pathology, Vienna Biocenter, Dr Bohr Gasse 7, A 1030 Vienna, Austria
    Immunity 24:269-81. 2006
    ....
  33. ncbi Analysis of C-MYC function in normal cells via conditional gene-targeted mutation
    I M de Alboran
    Howard Hughes Medical Institute and Children s, Hospital, Center for Blood Research and Department of Genetics, Harvard Medical School, Boston, MA 02115, USA
    Immunity 14:45-55. 2001
    ..We discuss these findings with respect to potential c-Myc functions in proliferation and apoptosis and also discuss potential limitations in the Cre-mediated gene inactivation approach...
  34. ncbi Development and maintenance of B and T lymphocytes requires antiapoptotic MCL-1
    Joseph T Opferman
    Howard Hughes Medical Institute, Dana Farber Cancer Institute, Department of Pathology and Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nature 426:671-6. 2003
    ..Thus, MCL-1, which selectively inhibits the proapoptotic protein BIM, is essential both early in lymphoid development and later on in the maintenance of mature lymphocytes...
  35. ncbi CD19 function in early and late B cell development. II. CD19 facilitates the pro-B/pre-B transition
    Dennis C Otero
    Division of Biology and University of California San Diego Cancer Center, La Jolla, CA 92093, USA
    J Immunol 171:5921-30. 2003
    ..b>CD19 promotes the proliferation and survival of mature B cells, but its role in early B cell development is less well ..
  36. ncbi GATA-3 regulates the development and function of invariant NKT cells
    Peter J Kim
    Division of Rheumatology, Immunology, and Allergy, Department of Medicine, Brigham and Women s Hospital, Boston, MA 02115, USA
    J Immunol 177:6650-9. 2006
    ..In addition, GATA-3 is also required for survival, activation, and effector functions of this unique population of T cells. Our data also reveal a previously unidentified peripheral maturation step that is GATA-3 dependent...
  37. ncbi Cloning of a mouse beta 1,3 N-acetylglucosaminyltransferase GlcNAc(beta 1,3)Gal(beta 1,4)Glc-ceramide synthase gene encoding the key regulator of lacto-series glycolipid biosynthesis
    T R Henion
    Eunice Kennedy Shriver Center, University of Massachusetts Medical School, Waltham, Massachusetts 02452, USA
    J Biol Chem 276:30261-9. 2001
    ..These data support a key role for the Lc3 synthase in regulating neolacto-series glycolipid synthesis during embryonic development...
  38. doi Type I interferon signaling in dendritic cells stimulates the development of lymph-node-resident T follicular helper cells
    Helena Cucak
    Immunology Section, BMC D14, Lund University, Lund 22184, Sweden
    Immunity 31:491-501. 2009
    ..Thus, our results identify type I interferon as a natural adjuvant that selectively supports the generation of lymph node resident Tfh cells...
  39. pmc Unique and independent roles for MLL in adult hematopoietic stem cells and progenitors
    Craig D Jude
    Department of Genetics and Norris Cotton Cancer Center, Dartmouth Medical School, 725 Remsen, HB7400, Hanover, NH 03755, USA
    Cell Stem Cell 1:324-37. 2007
    ..These studies demonstrate that Mll plays selective and independent roles within the hematopoietic system, maintaining quiescence in HSCs and promoting proliferation in progenitors...
  40. ncbi CD19 expression levels regulate B lymphocyte development: human CD19 restores normal function in mice lacking endogenous CD19
    S Sato
    Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA
    J Immunol 158:4662-9. 1997
    ..The effects of altered signaling thresholds in B lymphocytes were examined in CD19-deficient mice and transgenic mice that expressed human CD19 at varying densities...
  41. ncbi Notch-RBP-J signaling is involved in cell fate determination of marginal zone B cells
    Kenji Tanigaki
    Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Yoshida Konoe, Sakyo ku, Kyoto, 606 8501, Japan
    Nat Immunol 3:443-50. 2002
    ..In contrast, these mice exhibited increased mortality rates after blood-borne bacterial infection, which indicates that MZB cells play pivotal roles in the clearance of these bacteria...
  42. ncbi Type I IFN-mediated protection of macrophages and dendritic cells secures control of murine coronavirus infection
    Luisa Cervantes-Barragan
    Research Department, Kantonal Hospital St Gallen, St Gallen, Switzerland
    J Immunol 182:1099-106. 2009
    ....
  43. ncbi Pten inactivation alters peripheral B lymphocyte fate and reconstitutes CD19 function
    Amy N Anzelon
    Division of Biological Sciences, University of California, San Diego, 9500 Gilman Drive, MC 0322, La Jolla, CA 92093, USA
    Nat Immunol 4:287-94. 2003
    ..Inactivation of PTEN rescued germinal center, MZ B and B1 cell formation in CD19-/- mice, arguing that recruitment and activation of PI3K are the dominant roles for CD19 in these B cell ..
  44. pmc Cannabinoid receptor 2 mediates the retention of immature B cells in bone marrow sinusoids
    Joao P Pereira
    Howard Hughes Medical Institute and Department of Microbiology and Immunology, University of California San Francisco, USA
    Nat Immunol 10:403-11. 2009
    ..Our findings identify unique requirements for the retention of B cells in the bone marrow sinusoidal niche and suggest involvement of CB2 in the generation of the B cell repertoire...
  45. doi A regulatory B cell subset with a unique CD1dhiCD5+ phenotype controls T cell-dependent inflammatory responses
    Koichi Yanaba
    Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA
    Immunity 28:639-50. 2008
    ..In this study, T cell-mediated inflammation was exaggerated in CD19-deficient (Cd19(-/-)) mice and wild-type mice depleted of CD20(+) B cells, whereas inflammation was substantially ..
  46. pmc Critical roles of Pten in B cell homeostasis and immunoglobulin class switch recombination
    Akira Suzuki
    Department of Molecular Cell Biology, Research Institute for Microbial Disease, Osaka University, Osaka 565 0871, Japan
    J Exp Med 197:657-67. 2003
    ..Thus, Pten plays a role in developmental fate determination of B cells and is an indispensable regulator of B cell homeostasis...
  47. ncbi Notch2 is preferentially expressed in mature B cells and indispensable for marginal zone B lineage development
    Toshiki Saito
    Department of Hematology and Oncology, Graduate School of Medicine, University of Tokyo, Japan
    Immunity 18:675-85. 2003
    ..Among Notch target genes, the expression level of Deltex1 is prominent in MZB cells and strictly dependent on that of Notch2, suggesting that Deltex1 may play a role in MZB cell differentiation...
  48. ncbi Blimp-1 is required for the formation of immunoglobulin secreting plasma cells and pre-plasma memory B cells
    Miriam Shapiro-Shelef
    Department of Microbiology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA
    Immunity 19:607-20. 2003
    ..B cells lacking Blimp-1 cannot secrete Ig or induce muS mRNA when stimulated ex vivo. Furthermore, although prdm1-/- B cells fail to induce XBP-1, XBP-1 cannot rescue plasmacytic differentiation without Blimp-1...
  49. ncbi Critical roles for Rac1 and Rac2 GTPases in B cell development and signaling
    Marita J Walmsley
    Division of Immune Cell Biology, National Institute for Medical Research, The Ridgeway, Mill Hill, London, NW7 1AA, UK
    Science 302:459-62. 2003
    ..Both GTPases were required to transduce BCR signals leading to proliferation, survival and up-regulation of BAFF-R, a receptor for BAFF, a key survival molecule required for B cell development and maintenance...
  50. pmc The role of CXCR4 in maintaining peripheral B cell compartments and humoral immunity
    Yuchun Nie
    Dept of Microbiology, Columbia University, 701 West 168th St, HHSC 1406, New York, NY 10032, USA
    J Exp Med 200:1145-56. 2004
    ..These findings establish an important role for CXCR4 in regulating homeostasis of B cell compartmentalization and humoral immunity...
  51. ncbi Structure and domain organization of the CD19 antigen of human, mouse, and guinea pig B lymphocytes. Conservation of the extensive cytoplasmic domain
    L J Zhou
    Division of Tumor Immunology, Dana Farber Cancer Institute, Boston, MA 02115 6084
    J Immunol 147:1424-32. 1991
    The CD19 molecule is a 95,000 Mr cell-surface protein of human B lymphocytes with two extracellular Ig-like domains and a 240 amino acid cytoplasmic tail...
  52. ncbi Pax5/BSAP maintains the identity of B cells in late B lymphopoiesis
    M Horcher
    Research Institute of Molecular Pathology, Vienna Biocenter, Dr Bohr Gasse 7, A 1030 Vienna, Austria
    Immunity 14:779-90. 2001
    ..its late function, we generated a mouse strain carrying a floxed Pax5 allele that was conditionally inactivated by CD19-cre or Mx-cre expression...
  53. ncbi Vav-dependent and vav-independent phosphatidylinositol 3-kinase activation in murine B cells determined by the nature of the stimulus
    Elena Vigorito
    Laboratory of Lymphocyte Signaling and Development, Molecular Immunology Programme, Babraham Institute, Babraham, Cambridge, United Kingdom
    J Immunol 173:3209-14. 2004
    ..We show in this study that B cell activation following high avidity ligation of IgM or coligation of membrane Ig with CD19 elicits similar levels of Ca(2+) flux using different mechanisms...
  54. ncbi Distinct signaling requirements for Dmu selection, IgH allelic exclusion, pre-B cell transition, and tumor suppression in B cell progenitors
    Katsuhiko Hayashi
    Division of Molecular Biology, Research Institute for Biological Sciences, Tokyo University of Science, Yamazaki 2669, Noda, 278 0022, Chiba, Japan
    Immunity 18:825-36. 2003
    ..Here we show complete arrest of B cell development at the pre-B cell transition in BASH/CD19 double mutant mice, indicating partial redundancy of the two B cell-specific adaptors...
  55. doi Activation of the small GTPase Rac2 via the B cell receptor regulates B cell adhesion and immunological-synapse formation
    Eloisa Arana
    Lymphocyte Interaction Laboratory, Cancer Research UK, London Research Institute, Lincoln s Inn Fields Laboratories, 44 Lincoln s Inn Fields, London WC2A 3PX, UK
    Immunity 28:88-99. 2008
    ..We postulate that this critical role for Rac2 in mediating B cell adhesion and IS formation might apply in all lymphocytes...
  56. pmc Antiviral protection and germinal center formation, but impaired B cell memory in the absence of CD19
    T Fehr
    Institute of Experimental Immunology, Department of Pathology, University Hospital, CH 8091 Zurich, Switzerland
    J Exp Med 188:145-55. 1998
    Coligation of CD19, a molecule expressed during all stages of B cell development except plasmacytes, lowers the threshold for B cell activation with anti-IgM by a factor of 100...
  57. pmc The CD19 signal transduction molecule is a response regulator of B-lymphocyte differentiation
    S Sato
    Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA
    Proc Natl Acad Sci U S A 92:11558-62. 1995
    The phenotypes of CD19-deficient (CD19-/-) mice, and human CD19-transgenic (hCD19TG) mice that overexpress CD19 indicate that CD19 is a response regulator of B-lymphocyte surface receptor signaling...
  58. pmc Parasite-induced TH1 cells and intestinal dysbiosis cooperate in IFN-γ-dependent elimination of Paneth cells
    Megan Raetz
    Department of Immunology, University of Texas Southwestern Medical Center, Dallas, Texas, USA
    Nat Immunol 14:136-42. 2013
    ..gondii infection identified the T cell-intrinsic TLR pathway as a major regulator of IFN-γ production in CD4(+) T cells responsible for Paneth cell death, dysbiosis and intestinal immunopathology...
  59. pmc Critical role for mouse marginal zone B cells in PF4/heparin antibody production
    Yongwei Zheng
    Blood Research Institute, BloodCenter of Wisconsin, 8727 Watertown Plank Rd, Milwaukee, WI 53226, USA
    Blood 121:3484-92. 2013
    ..Taken together, these data demonstrate that MZ B cells are critical for PF4/heparin-specific antibody production...
  60. pmc ZBTB32 is an early repressor of the CIITA and MHC class II gene expression during B cell differentiation to plasma cells
    Hye Suk Yoon
    Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA
    J Immunol 189:2393-403. 2012
    ..These results introduce ZBTB32 as a novel regulator of MHC-II gene expression and a potential regulatory partner of Blimp-1 in repressing gene expression...
  61. pmc Expression of p16(INK4a) prevents cancer and promotes aging in lymphocytes
    Yan Liu
    Department of Genetics, The Lineberger Comprehensive Cancer Center, The University of North Carolina School of Medicine, Chapel Hill, NC 27599 7295, USA
    Blood 117:3257-67. 2011
    ..Together, these data show that expression of p16(INK4a) can promote aging and prevent cancer in related lymphoid progeny of a common stem cell...
  62. doi Monocytes/macrophages and/or neutrophils are the target of IL-10 in the LPS endotoxemia model
    Marina C Pils
    Department of Experimental Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany
    Eur J Immunol 40:443-8. 2010
    ..In contrast, in an IL-10-regulated T-cell response to Trichuris muris infection, IL-10 acting on T cells or monocytes/macrophages/neutrophils is not critical for the control of the infection...
  63. pmc Phospholipase C-gamma2 and Vav cooperate within signaling microclusters to propagate B cell spreading in response to membrane-bound antigen
    Michele Weber
    Lymphocyte Interaction Laboratory, London Research Institute, Cancer Research UK, London WC2A 3PX, England, UK
    J Exp Med 205:853-68. 2008
    ..Thus, we demonstrate the importance of cooperation between components of the microsignalosome in the amplification of signaling and propagation of B cell spreading, which is critical for appropriate B cell activation...
  64. doi Critical role of Pcid2 in B cell survival through the regulation of MAD2 expression
    Teruo Nakaya
    Department of Immunology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
    J Immunol 185:5180-7. 2010
    ..b>Cd19-cre-derived targeting of the Pcid2 gene induced a mature B cell deficiency in mice...
  65. pmc Macrophage IL-12p70 signaling prevents HSV-1-induced CNS autoimmunity triggered by autoaggressive CD4+ Tregs
    Kevin R Mott
    Center for Neurobiology and Vaccine Development, Ophthalmology Research, Department of Surgery and Regenerative Medicine Institute, Cedars Sinai Medical Center, Los Angeles, California, USA
    Invest Ophthalmol Vis Sci 52:2321-33. 2011
    ..However, it is unclear whether innate immune cells modulate Treg function. Here the authors examined the role of innate immunity in lymphomyeloid homeostasis...
  66. pmc NK cells in the CD19- B220+ bone marrow fraction are increased in senescence and reduce E2A and surrogate light chain proteins in B cell precursors
    Anne M King
    Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL 33101, USA
    Mech Ageing Dev 130:384-92. 2009
    ..Herein, we show that aged bone marrow has increased Hardy Fraction A (CD19(-) B220(+)) cells, including NK cells, that can inhibit both E47 (E2A) protein and surrogate light chain protein ..
  67. doi p75 Neurotrophin receptor is a marker for precursors of stellate cells and portal fibroblasts in mouse fetal liver
    Kaori Suzuki
    Institute of Molecular and Cellular Biosciences, University of Tokyo, Tokyo, Japan
    Gastroenterology 135:270-281.e3. 2008
    ..HSCs and PFs play pivotal roles in liver regeneration and fibrosis. However, the roles of mesenchymal cells in fetal liver remain poorly understood. In this study, we aimed to characterize mesenchymal cells in mouse fetal liver...
  68. doi Instructive role of the transcription factor E2A in early B lymphopoiesis and germinal center B cell development
    Kyongrim Kwon
    Research Institute of Molecular Pathology, Vienna Biocenter, Dr Bohr Gasse 7, A 1030 Vienna, Austria
    Immunity 28:751-62. 2008
    ....
  69. pmc Ablation of PI3K blocks BCR-ABL leukemogenesis in mice, and a dual PI3K/mTOR inhibitor prevents expansion of human BCR-ABL+ leukemia cells
    Michael G Kharas
    Department of Molecular Biology and Biochemistry, Center for Immunology, University of California, Irvine, Irvine, California, USA
    J Clin Invest 118:3038-50. 2008
    ..PI3K and mTOR, PI-103, was more effective than rapamycin at suppressing proliferation of mouse pre-B-ALL and human CD19+CD34+)Ph+ ALL leukemia cells treated with the ABL kinase inhibitor imatinib...
  70. pmc A critical role of TAK1 in B-cell receptor-mediated nuclear factor kappaB activation
    James Schuman
    Blood Research Institute, BloodCenter of Wisconsin, Milwaukee 53226, USA
    Blood 113:4566-74. 2009
    ..Importantly, TAK1-deficient B cells failed to activate NF-kappaB after BCR stimulation. Thus, TAK1 is critical for B-cell maturation and BCR-induced NF-kappaB activation...
  71. doi B-cell responses to B-cell activation factor of the TNF family (BAFF) are impaired in the absence of PI3K delta
    Thomas Henley
    Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Cambridge, UK
    Eur J Immunol 38:3543-8. 2008
    ..Our findings reveal an important role for p110delta in regulating B-cell responses to BAFF...
  72. ncbi BAFF binding to T cell-expressed BAFF-R costimulates T cell proliferation and alloresponses
    Qunrui Ye
    Department of Pathology and Laboratory Medicine, Joseph Stokes Jr Research Institute and Biesecker Pediatric Liver Center, The Children s Hospital of Philadelphia and the University of Pennsylvania, Philadelphia, PA 19104, USA
    Eur J Immunol 34:2750-9. 2004
    ..Taken together, these data indicate the BAFF/BAFF-R pathway contributes to both T and B cell responses and may be an attractive target for control of acute and chronic allograft rejection...
  73. ncbi Distinct and nonredundant in vivo functions of TNF produced by t cells and macrophages/neutrophils: protective and deleterious effects
    Sergei I Grivennikov
    Laboratory of Molecular Immunology, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences and Belozersky Institute of Physico Chemical Biology, 32 Vavilov Str, 119991 Moscow, Russia
    Immunity 22:93-104. 2005
    ..Our data suggest that T-cell-specific TNF ablation may provide a therapeutic advantage over systemic blockade...
  74. pmc IkappaB kinase signaling is essential for maintenance of mature B cells
    Manolis Pasparakis
    Institute for Genetics, University of Cologne, D 50931 Cologne, Germany
    J Exp Med 196:743-52. 2002
    ..We conclude that maintenance of mature B cells depends on IKK-mediated activation of NF-kappaB...
  75. pmc Role of T and NK cells and IL7/IL7r interactions during neonatal maturation of lymph nodes
    Mark C Coles
    Division of Molecular Immunology and Immune Cell Biology and Confocal Microscopy and Image Analysis Laboratory, National Institute for Medical Research, Mill Hill, London, United Kingdom
    Proc Natl Acad Sci U S A 103:13457-62. 2006
    ..Thus, we reveal a unique stage of postnatal LN development during which mature lymphocytes and IL7/IL7r interactions may play an important role...
  76. ncbi Gene expression analysis of myeloid and lymphoid lineage markers during mouse haematopoiesis
    E Sakhinia
    Division of Laboratory and Regenerative Medicine, School of Medicine, Faculty of Medical and Human Sciences, The University of Manchester, Manchester, UK
    Br J Haematol 135:105-16. 2006
    ..To overcome this, the expression profile of lymphoid and myeloid-associated genes (LEF1, EBF, CD19, Sox-4, B29, CD45, C-fms, lysozyme, PU...
  77. ncbi The first 3 days of B-cell development in the mouse embryo
    Belen de Andres
    Centro Nacional de Microbiologia, Instituto de Salud Carlos III ISCIII, Majadahonda, Spain
    Blood 100:4074-81. 2002
    ..We describe here a population of c-kit(+)AA4.1(+)CD19(+)Pax5(+) cells present in the aorta-gonad-mesonephros (AGM) area and in the livers of 11-dpc mouse embryos...
  78. ncbi Loss of tolerance of anti-dsDNA B cells in mice overexpressing CD19
    Devon K Taylor
    Department of Biochemistry, The Graduate Program in Biochemistry, The City College of New York, The Graduate Center, CUNY, New York, NY 10016, USA
    Mol Immunol 43:1776-90. 2006
    ..In C57BL/6 mice overexpressing CD19, a molecule, which lowers the threshold for B cell activation, elevated levels of serum autoantibodies have been ..
  79. ncbi Impaired assembly of the major histocompatibility complex class I peptide-loading complex in mice deficient in the oxidoreductase ERp57
    Natalio Garbi
    Division of Molecular Immunology, German Cancer Research Center DKFZ, 69120 Heidelberg, Germany
    Nat Immunol 7:93-102. 2006
    ..Our results indicate that ERp57 does not influence the redox state of MHC class I molecules but is an essential structural component required for stable assembly of the peptide-loading complex...
  80. ncbi CD22: a multifunctional receptor that regulates B lymphocyte survival and signal transduction
    Thomas F Tedder
    Department of Immunology, Duke University Medical Center, Durham, North Carolina 27710, USA
    Adv Immunol 88:1-50. 2005
    ..complex role for CD22 has recently emerged, including a central role in a novel regulatory loop controlling the CD19/CD21-Src-family protein tyrosine kinase (PTK) amplification pathway that regulates basal signaling thresholds and ..
  81. ncbi Role of antigen receptor affinity in T cell-independent antibody responses in vivo
    Tien An Yang Shih
    Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10021, USA
    Nat Immunol 3:399-406. 2002
    ..However, in competition experiments only the high-affinity B cells responded to antigen. CD19 deficiency increased the affinity threshold of TI-2 responses, whereas Lyn deficiency enhanced clonal expansion but ..
  82. pmc Extracellular signal-regulated protein kinase 2 is required for efficient generation of B cells bearing antigen-specific immunoglobulin G
    Hideki Sanjo
    Laboratory for Lymphocyte Differentiation, RIKEN Research Center for Allergy and Immunology, Tsurumi ku, Yokohama, Kanagawa 230 0045, Japan
    Mol Cell Biol 27:1236-46. 2007
    ..Notably, this defect was countered by overexpression of the antiapoptotic factor Bcl-2. Together, our results suggest that ERK2 plays a key role in efficient generation of antigen-specific IgG-bearing B cells by promoting their survival...
  83. ncbi Structure of the genes encoding the CD19 antigen of human and mouse B lymphocytes
    L J Zhou
    Division of Tumor Immunology, Dana Farber Cancer Institute, Boston, MA
    Immunogenetics 35:102-11. 1992
    b>CD19 is a B lymphocyte cell-surface marker that is expressed early during pre-B-cell differentiation with expression persisting until terminal differentiation into plasma cells...
  84. pmc B-cell development fails in the absence of the Pbx1 proto-oncogene
    Mrinmoy Sanyal
    Department of Pathology, Stanford University, School of Medicine, Stanford, CA 94305, USA
    Blood 109:4191-9. 2007
    ..Conditional inactivation of Pbx1 in pro-B (CD19(+)) cells and thereafter revealed that Pbx1 is not necessary for B-cell development to proceed from the pro-B-cell ..
  85. ncbi Excision of the Frt-flanked neo (R) cassette from the CD19cre knock-in transgene reduces Cre-mediated recombination
    Marc Schmidt-Supprian
    The CBR Institute for Biomedical Research, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA
    Transgenic Res 16:657-60. 2007
    ..In addition our findings suggest that gene expression from the CD19 locus can be increased by the insertion of exogenous enhancer sequences, without compromising B cell specificity.
  86. pmc CD19 expression in B cells is important for suppression of contact hypersensitivity
    Rei Watanabe
    Department of Dermatology, Faculty of Medicine, University of Tokyo, Tokyo, Japan
    Am J Pathol 171:560-70. 2007
    ..However, recent reports have suggested pivotal roles of B cells in CHS. CD19 serves as a positive B-cell response regulator that defines signaling thresholds critical for B-cell responses...
  87. pmc Impaired CD19 expression and signaling, enhanced antibody response to type II T independent antigen and reduction of B-1 cells in CD81-deficient mice
    E N Tsitsikov
    Children s Hospital and Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 94:10844-9. 1997
    The tetraspanin CD81 is ubiquitously expressed and associated with CD19 on B lymphocytes and with CD4 and CD8 on T lymphocytes...
  88. pmc A subpopulation of B220+ cells in murine bone marrow does not express CD19 and contains natural killer cell progenitors
    A Rolink
    Basel Institute for Immunology, Switzerland
    J Exp Med 183:187-94. 1996
    ..mice contains a small population of B220(CD45R)+ cells, which do not express the B lineage marker CD19. Instead, part of this population coexpresses the surface marker CD43 and lacks or expresses very low levels of ..
  89. ncbi Regulation of B lymphocyte development and activation by the CD19/CD21/CD81/Leu 13 complex requires the cytoplasmic domain of CD19
    S Sato
    Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA
    J Immunol 159:3278-87. 1997
    B lymphocyte development and function are regulated in part by the CD19 cell surface receptor complex, which is composed of at least four proteins; CD19, CD21 (CR2, complement receptor 2), CD81, and Leu 13...
  90. doi The DLEU2/miR-15a/16-1 cluster controls B cell proliferation and its deletion leads to chronic lymphocytic leukemia
    Ulf Klein
    Institute for Cancer Genetics and the Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY 10032, USA
    Cancer Cell 17:28-40. 2010
    ..miR-15a/16-1-deletion accelerates the proliferation of both human and mouse B cells by modulating the expression of genes controlling cell-cycle progression. These results define the role of 13q14 deletions in the pathogenesis of CLL...
  91. pmc Genetic dissection of the cellular pathways and signaling mechanisms in modeled tumor necrosis factor-induced Crohn's-like inflammatory bowel disease
    Dimitris Kontoyiannis
    Institute for Immunology, Biomedical Sciences Research Center Al Fleming, Vari 166 72, Greece Division of Gastroenterology and Hepatology, University of Virginia Health Sciences Center, Charlottesville, VA 22906, USA
    J Exp Med 196:1563-74. 2002
    ..Our data establish the existence of redundant cellular pathways operating downstream of TNF in inflammatory bowel disease, and demonstrate the therapeutic potential of selective kinase blockade in TNF-mediated intestinal pathology...
  92. ncbi The role of the CD19/CD21 complex in B cell processing and presentation of complement-tagged antigens
    A Cherukuri
    National Institute of Allergy and Infectious Diseases, Laboratory of Immunogenetics, National Institutes of Health, Rockville, MD 20852, USA
    J Immunol 167:163-72. 2001
    The CD19/CD21 complex is an essential B cell coreceptor that functions synergistically to enhance signaling through the B cell Ag receptor in response to T cell-dependent, complement-tagged Ags...
  93. pmc A sensitized genetic system for the analysis of murine B lymphocyte signal transduction pathways dependent on Bruton's tyrosine kinase
    A B Satterthwaite
    Department of Microbiology, Immunology, and Molecular Genetics, and Howard Hughes Medical Institute, University of California, Los Angeles, CA 90095, USA
    Proc Natl Acad Sci U S A 97:6687-92. 2000
    ..homolog), or SH2-containing inositol phosphatase suppressed the Btk(lo) phenotype in vitro but not in vivo, whereas CD19 and the p85alpha form of phosphoinositide 3-kinase behaved as Btk(lo) enhancers in vivo but not in vitro...
  94. ncbi CD19 regulates Src family protein tyrosine kinase activation in B lymphocytes through processive amplification
    M Fujimoto
    Department of Immunology, Duke University Medical Center, Durham, North Carolina 27710, USA
    Immunity 13:47-57. 2000
    b>CD19 regulates constitutive and antigen receptor-induced signaling thresholds in B lymphocytes through its unique cytoplasmic domain...
  95. ncbi A population of CD19highCD45R-/lowCD21low B lymphocytes poised for spontaneous secretion of IgG and IgA antibodies
    Belen de Andres
    Centro Nacional de Microbiologia, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain
    J Immunol 179:5326-34. 2007
    ..The earliest B lineage-restricted precursors in gestational day 11 mouse embryos display the CD19(+)CD45R/B220(-) phenotype...
  96. ncbi Coligation of the B cell receptor with complement receptor type 2 (CR2/CD21) using its natural ligand C3dg: activation without engagement of an inhibitory signaling pathway
    Taras Lyubchenko
    Department of Medicine, University of Colorado Health Sciences Center, Denver, CO 80220, USA
    J Immunol 174:3264-72. 2005
    ....
  97. ncbi CD19 regulates B cell maturation, proliferation, and positive selection in the FDC zone of murine splenic germinal centers
    Yue Wang
    Department of Medicine, The University of Alabama at Birmingham, Birmingham, Alabama 35294, USA
    Immunity 22:749-61. 2005
    Mice with mutations in CD19 Y482/Y513 form germinal centers (GC) but fail to produce high-affinity antibodies. In these mice, GC B cell differentiation, proliferation, and class switching occur but are defective...
  98. doi TRAF2 and TRAF3 signal adapters act cooperatively to control the maturation and survival signals delivered to B cells by the BAFF receptor
    Sandra Gardam
    Garvan Institute of Medical Research, 384 Victoria St, Darlinghurst NSW 2010, Australia
    Immunity 28:391-401. 2008
    ..This process was TRAF2 dependent, revealing dual roles for TRAF2 in regulating B cell homeostasis...
  99. pmc Transcription factor Mef2c is required for B cell proliferation and survival after antigen receptor stimulation
    Peter R Wilker
    Department of Pathology and Center for Immunology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Nat Immunol 9:603-12. 2008
    ..Mef2c-dependent targets included the genes encoding cyclin D2 and the prosurvival factor Bcl-x(L). Our results emphasize an unrecognized but critical function for Mef2c in BCR signaling...
  100. ncbi Essential role for caspase-8 in Toll-like receptors and NFkappaB signaling
    Benedicte Lemmers
    Ontario Cancer Institute, University of Toronto, Toronto, Ontario M5G 2C1, Canada
    J Biol Chem 282:7416-23. 2007
    ..Our study supports dual roles for caspase-8 in apoptotic and nonapoptotic functions and demonstrates its requirement for TLR signaling and in the regulation of NFkappaB function...
  101. ncbi Serum response factor contributes selectively to lymphocyte development
    Anne Fleige
    Department of Experimental Immunology, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany
    J Biol Chem 282:24320-8. 2007
    ..Our study also revealed a contribution of SRF to the expression of the surface molecules IgM, CD19, and the chemokine receptor 4 in B lymphocytes...

Research Grants3

  1. Effect of Antibodies/Chemotherapy on Childhood Leukemia
    LARRY HERRERA; Fiscal Year: 2007
    ..We will then develop new treatment regimens for children with multiply relapsed leukemia based on this information. ..
  2. Regulation of T cell activation and tolerance by Grail
    ROZA INSAFETDINOVNA NURIEVA; Fiscal Year: 2010
    ..These proposed studies will greatly advance our knowledge on Grail function in T cells and will provide a novel and unique insight into proper T cell regulation that governs self tolerance and immune function. ..