germinal center

Summary

Summary: The activated center of a lymphoid follicle in secondary lymphoid tissue where B-LYMPHOCYTES are stimulated by antigens and helper T cells (T-LYMPHOCYTES, HELPER-INDUCER) are stimulated to generate memory cells.

Top Publications

  1. Thieblemont C, Briere J, Mounier N, Voelker H, Cuccuini W, Hirchaud E, et al. The germinal center/activated B-cell subclassification has a prognostic impact for response to salvage therapy in relapsed/refractory diffuse large B-cell lymphoma: a bio-CORAL study. J Clin Oncol. 2011;29:4079-87 pubmed publisher
  2. Jones S, White C, Robb L, Alexander W, Tarlinton D. SOCS3 deletion in B cells alters cytokine responses and germinal center output. J Immunol. 2011;187:6318-26 pubmed publisher
    ..IL-6 stimulation of plasma cells and, in a T cell-dependent immunization model, reduced the number of germinal center B cells formed and altered the production of Ag-specific IgM and IgE...
  3. Habara T, Sato Y, Takata K, Iwaki N, Okumura H, Sonobe H, et al. Germinal center B-cell-like versus non-germinal center B-cell-like as important prognostic factor for localized nodal DLBCL. J Clin Exp Hematop. 2012;52:91-9 pubmed
    ..the prognostic significance of 39 Japanese patients with localized nodal DLBCL with special reference to the germinal center B-cell-like (GCB) versus non-germinal center B-cell-like (NGCB) types...
  4. Lu K, Kanno Y, Cannons J, Handon R, Bible P, Elkahloun A, et al. Functional and epigenetic studies reveal multistep differentiation and plasticity of in vitro-generated and in vivo-derived follicular T helper cells. Immunity. 2011;35:622-32 pubmed publisher
    Follicular T helper (Tfh) cells provide critical help to B cells for germinal center (GC) formation...
  5. Bollig N, Brüstle A, Kellner K, Ackermann W, Abass E, Raifer H, et al. Transcription factor IRF4 determines germinal center formation through follicular T-helper cell differentiation. Proc Natl Acad Sci U S A. 2012;109:8664-9 pubmed publisher
    Follicular T-helper (T(FH)) cells cooperate with GL7(+)CD95(+) germinal center (GC) B cells to induce antibody maturation...
  6. Khalil A, Cambier J, Shlomchik M. B cell receptor signal transduction in the GC is short-circuited by high phosphatase activity. Science. 2012;336:1178-81 pubmed publisher
    ..Furthermore, SHP-1 was required for GC maintenance. Intriguingly, GC B cells in the cell-cycle G(2) period regained responsiveness to BCR stimulation. These data have implications for how higher-affinity B cells are selected in the GC...
  7. Green B, Belcheva A, Nepal R, Boulianne B, Martin A. The mismatch repair pathway functions normally at a non-AID target in germinal center B cells. Blood. 2011;118:3013-8 pubmed publisher
    ..By contrast, Msh2 deficiency in germinal center (GC) B cells decreases the mutation frequency at the IgH V region as a dU:dG mismatch produced by AID ..
  8. Bentebibel S, Schmitt N, Banchereau J, Ueno H. Human tonsil B-cell lymphoma 6 (BCL6)-expressing CD4+ T-cell subset specialized for B-cell help outside germinal centers. Proc Natl Acad Sci U S A. 2011;108:E488-97 pubmed publisher
    ..Collectively, our study indicates that CXCR5(lo)ICOS(lo) CD4(+) T cells in human tonsils represent Tfh lineage-committed cells that provide help to naïve and memory B cells outside GCs...
  9. Calado D, Sasaki Y, Godinho S, Pellerin A, Köchert K, Sleckman B, et al. The cell-cycle regulator c-Myc is essential for the formation and maintenance of germinal centers. Nat Immunol. 2012;13:1092-100 pubmed publisher
    ..As these translocations are generally dependent on transcription of the recombining partner loci, the c-Myc(+) GC subpopulations may be at a particularly high risk for malignant transformation...

Scientific Experts

More Information

Publications62

  1. Harker J, Lewis G, Mack L, Zuniga E. Late interleukin-6 escalates T follicular helper cell responses and controls a chronic viral infection. Science. 2011;334:825-9 pubmed publisher
    ..This resulted in escalation of germinal center reactions and improved antibody responses...
  2. Moisini I, Huang W, Bethunaickan R, Sahu R, Ricketts P, Akerman M, et al. The Yaa locus and IFN-? fine-tune germinal center B cell selection in murine systemic lupus erythematosus. J Immunol. 2012;189:4305-12 pubmed publisher
    ..Vk5-43 and Vk5-48, which were rare in the naive repertoire, were markedly overrepresented in the germinal center repertoire of both males and females, but the VJ junctions differed between males and females with higher-..
  3. Linterman M, Liston A, Vinuesa C. T-follicular helper cell differentiation and the co-option of this pathway by non-helper cells. Immunol Rev. 2012;247:143-59 pubmed publisher
    ..of Tfh cells into follicles and modulates their cytokine expression profile so they can support and select germinal center B cells that have acquired affinity-enhancing mutations in their immunoglobulin genes...
  4. Krautler N, Kana V, Kranich J, Tian Y, Perera D, Lemm D, et al. Follicular dendritic cells emerge from ubiquitous perivascular precursors. Cell. 2012;150:194-206 pubmed publisher
    ..The ubiquity of preFDC and their strategic location at blood vessels may explain the de novo generation of organized lymphoid tissue at sites of lymphocytic inflammation...
  5. Dominguez Sola D, Victora G, Ying C, Phan R, Saito M, Nussenzweig M, et al. The proto-oncogene MYC is required for selection in the germinal center and cyclic reentry. Nat Immunol. 2012;13:1083-91 pubmed publisher
    ..Inhibition of c-Myc in vivo led to GC collapse, which indicated an essential role for c-Myc in GCs. Our results have implications for the mechanism of GC selection and the role of c-Myc in lymphomagenesis...
  6. Bannard O, Horton R, Allen C, An J, Nagasawa T, Cyster J. Germinal center centroblasts transition to a centrocyte phenotype according to a timed program and depend on the dark zone for effective selection. Immunity. 2013;39:912-24 pubmed publisher
    b>Germinal center (GC) B cells cycle between the dark zone (DZ) and light zone (LZ) during antibody affinity maturation. Whether this movement is necessary for GC function has not been tested...
  7. Espéli M, Clatworthy M, Bökers S, Lawlor K, Cutler A, Köntgen F, et al. Analysis of a wild mouse promoter variant reveals a novel role for FcγRIIb in the control of the germinal center and autoimmunity. J Exp Med. 2012;209:2307-19 pubmed publisher
    ..in the absence of an AP-1-binding site in its promoter, FcγRIIb failed to be up-regulated on activated and germinal center (GC) B cells...
  8. Taylor J, Pape K, Jenkins M. A germinal center-independent pathway generates unswitched memory B cells early in the primary response. J Exp Med. 2012;209:597-606 pubmed publisher
    Memory B cells can be produced from the classical germinal center (GC) pathway or a less understood GC-independent route...
  9. Taylor J, Jenkins M, Pape K. Heterogeneity in the differentiation and function of memory B cells. Trends Immunol. 2012;33:590-7 pubmed publisher
    ..Recent studies have revealed novel insights into the differentiation and function of these cells, and have shown that the memory B cell pool is much more heterogeneous than previously appreciated...
  10. Béguelin W, Popovic R, Teater M, Jiang Y, Bunting K, Rosén M, et al. EZH2 is required for germinal center formation and somatic EZH2 mutations promote lymphoid transformation. Cancer Cell. 2013;23:677-92 pubmed publisher
    The EZH2 histone methyltransferase is highly expressed in germinal center (GC) B cells and targeted by somatic mutations in B cell lymphomas...
  11. Green J, Cyster J. S1PR2 links germinal center confinement and growth regulation. Immunol Rev. 2012;247:36-51 pubmed publisher
    ..Herein, we detail present understanding of S1PR2 and S1P biology as it pertains to GC B cells and place this information in the context of a current model of GC function...
  12. Kunkalla K, Liu Y, Qu C, Leventaki V, Agarwal N, Singh R, et al. Functional inhibition of BCL2 is needed to increase the susceptibility to apoptosis to SMO inhibitors in diffuse large B-cell lymphoma of germinal center subtype. Ann Hematol. 2013;92:777-87 pubmed publisher
    ..lymphoma (DLBCL) cell lines of activated B-cell (ABC) type but predominantly cell cycle arrest in those of germinal center (GC)...
  13. King I, Fortier A, Tighe M, Dibble J, Watts G, Veerapen N, et al. Invariant natural killer T cells direct B cell responses to cognate lipid antigen in an IL-21-dependent manner. Nat Immunol. 2011;13:44-50 pubmed publisher
    ..Thus, cognate iNKT cell help for lipid-specific B cells induces a unique signature that is a hybrid of classic T cell-dependent and T cell-independent type 2 B cell responses. ..
  14. Richards K, Motsinger Reif A, Chen H, Fedoriw Y, Fan C, Nielsen D, et al. Gene profiling of canine B-cell lymphoma reveals germinal center and postgerminal center subtypes with different survival times, modeling human DLBCL. Cancer Res. 2013;73:5029-39 pubmed publisher
    ..Furthermore, immunoglobulin heavy chain ongoing mutation status, which is correlated with ABC/germinal center B-cell cell of origin in hDLBCL, separated cBCL into two groups with statistically different progression-free ..
  15. Wittenbrink N, Klein A, Weiser A, Schuchhardt J, Or Guil M. Is there a typical germinal center? A large-scale immunohistological study on the cellular composition of germinal centers during the hapten-carrier-driven primary immune response in mice. J Immunol. 2011;187:6185-96 pubmed publisher
    ..DZ and LZ differ in the T cell-to-macrophage ratio rather than in the density of T cells...
  16. Vinuesa C, Cyster J. How T cells earn the follicular rite of passage. Immunity. 2011;35:671-80 pubmed publisher
    ..This review will focus on recent insights into the early events that determine Tfh cell differentiation...
  17. Boyden A, Legge K, Waldschmidt T. Pulmonary infection with influenza A virus induces site-specific germinal center and T follicular helper cell responses. PLoS ONE. 2012;7:e40733 pubmed publisher
    ..Collectively, these findings reveal respiratory IAV infection to induce strong T helper cell-driven B cell responses in various organs, with each site displaying unique attributes...
  18. Gatto D, Wood K, Brink R. EBI2 operates independently of but in cooperation with CXCR5 and CCR7 to direct B cell migration and organization in follicles and the germinal center. J Immunol. 2011;187:4621-8 pubmed publisher
    ..Thus, EBI2-mediated chemotaxis provides a third dimension to B cell migration that balances and integrates with the inputs from CXCR5 and CCR7 to determine B cell positioning...
  19. Kawamoto S, Tran T, Maruya M, Suzuki K, Doi Y, Tsutsui Y, et al. The inhibitory receptor PD-1 regulates IgA selection and bacterial composition in the gut. Science. 2012;336:485-9 pubmed publisher
    ..T(FH)) cells with altered phenotypes, which results in dysregulated selection of IgA precursor cells in the germinal center of Peyer's patches...
  20. Ballesteros Tato A, León B, Graf B, Moquin A, Adams P, Lund F, et al. Interleukin-2 inhibits germinal center formation by limiting T follicular helper cell differentiation. Immunity. 2012;36:847-56 pubmed publisher
    ..promote T cell-dependent humoral immune responses by providing T cell help to B cells and by promoting germinal center (GC) formation and long-lived antibody responses...
  21. Donius L, Handy J, Weis J, Weis J. Optimal germinal center B cell activation and T-dependent antibody responses require expression of the mouse complement receptor Cr1. J Immunol. 2013;191:434-47 pubmed publisher
    ..Altogether, these data suggest that the production of Cr1, primarily by FDCs, is critical in the generation of appropriately activated B cells of the germinal center and the generation of mature Ab responses.
  22. Conlon T, Saeb Parsy K, Cole J, Motallebzadeh R, Qureshi M, Rehakova S, et al. Germinal center alloantibody responses are mediated exclusively by indirect-pathway CD4 T follicular helper cells. J Immunol. 2012;188:2643-52 pubmed publisher
    ..CD4 T cell help for GC alloantibody responses is provided exclusively via the indirect-allorecognition pathway. ..
  23. Johnston R, Choi Y, Diamond J, Yang J, Crotty S. STAT5 is a potent negative regulator of TFH cell differentiation. J Exp Med. 2012;209:243-50 pubmed publisher
    ..helper T cells (T(FH) cells) constitute the CD4(+) T cell subset that is specialized to provide help to germinal center (GC) B cells and, consequently, mediate the development of long-lived humoral immunity...
  24. Edlefsen K, Greisman H, Yi H, Mantei K, Fromm J. Early lymph node involvement by mantle cell lymphoma limited to the germinal center: report of a case with a novel "follicular in situ" growth pattern. Am J Clin Pathol. 2011;136:276-81 pubmed publisher
  25. McHeyzer Williams M, Okitsu S, Wang N, McHeyzer Williams L. Molecular programming of B cell memory. Nat Rev Immunol. 2011;12:24-34 pubmed publisher
    ..In this Review, we integrate this new information about each phase of antigen-specific B cell development to describe the newly unravelled molecular dynamics of memory B cell programming...
  26. Ochiai K, Maienschein Cline M, Simonetti G, Chen J, Rosenthal R, Brink R, et al. Transcriptional regulation of germinal center B and plasma cell fates by dynamical control of IRF4. Immunity. 2013;38:918-29 pubmed publisher
    ..We show IRF4 to be also required for generation of germinal center (GC) B cells...
  27. Hamel K, Liarski V, Clark M. Germinal center B-cells. Autoimmunity. 2012;45:333-47 pubmed publisher
    Within the B-cell follicle of secondary lymphoid organs, germinal center (GC) reactions produce high affinity antibody-secreting plasma cells (PCs) and memory B-cells necessary for the host's defense against invading pathogens...
  28. Good Jacobson K, Song E, Anderson S, Sharpe A, Shlomchik M. CD80 expression on B cells regulates murine T follicular helper development, germinal center B cell survival, and plasma cell generation. J Immunol. 2012;188:4217-25 pubmed publisher
    b>Germinal center (GC) B cells and T follicular helper (T(FH)) cells interact in the production of high-affinity long-lived plasma cells (PCs) and memory B cells, although the mechanisms regulating the formation of these long-lived ..
  29. Shin D, Lee C, Morse H. IRF8 governs expression of genes involved in innate and adaptive immunity in human and mouse germinal center B cells. PLoS ONE. 2011;6:e27384 pubmed publisher
    ..B cells into the splenic follicular and marginal zone compartments, and is expressed at highest levels in germinal center (GC) B cells...
  30. Ding Y, Li J, Wu Q, Yang P, Luo B, Xie S, et al. IL-17RA is essential for optimal localization of follicular Th cells in the germinal center light zone to promote autoantibody-producing B cells. J Immunol. 2013;191:1614-24 pubmed publisher
    ..These data suggest a novel concept that TFH differentiation and its stabilization in the LZ are two separate checkpoints and that IL-21 and IL-17 act at each checkpoint to enable pathogenic GC development. ..
  31. Browne E. Toll-like receptor 7 controls the anti-retroviral germinal center response. PLoS Pathog. 2011;7:e1002293 pubmed publisher
    ..in infected TLR7-deficient mice upregulated CD69 and CD86 early in infection, but failed to develop into germinal center B cells...
  32. Iqbal J, Meyer P, Smith L, Johnson N, Vose J, Greiner T, et al. BCL2 predicts survival in germinal center B-cell-like diffuse large B-cell lymphoma treated with CHOP-like therapy and rituximab. Clin Cancer Res. 2011;17:7785-95 pubmed publisher
    ..However, after the inclusion of rituximab (R) in the CHOP regimen, several conflicting observations about the prognostic value of BCL2 expression have been reported...
  33. He X, Li B, Yang S, Lu N, Zhang X, Zou S, et al. R-CHOP regimen can significantly decrease the risk of disease relapse and progression in patients with non-germinal center B-cell subtype diffuse large B-cell lymphoma. Chin J Cancer. 2012;31:306-14 pubmed publisher
    ..role of rituximab when added to the CHOP-like regimen in the treatment of immunohistochemically defined non-germinal center B-cell subtype (non-GCB) diffuse large B-cell lymphoma(DLBCL), 159 newly diagnosed DLBCL patients were ..
  34. Pasqualucci L, Trifonov V, Fabbri G, Ma J, Rossi D, Chiarenza A, et al. Analysis of the coding genome of diffuse large B-cell lymphoma. Nat Genet. 2011;43:830-7 pubmed publisher
    ..These results provide initial data on the complexity of the DLBCL coding genome and identify novel dysregulated pathways underlying its pathogenesis...
  35. Li J, Zhang W, Tang Y, Li G, Dong D. In situ follicular lymphoma with progressive transformation of the germinal centers confirmed by laser capture microdissection, IGH gene rearrangement analysis, and fluorescence in situ hybridization for t(14;18). Hum Pathol. 2012;43:138-43 pubmed publisher
    ..These findings suggest a case of multicentric in situ follicular lymphoma and provide new insights into the pathogenesis of this disease...
  36. Hua Z, Gross A, Lamagna C, Ramos Hernández N, Scapini P, Ji M, et al. Requirement for MyD88 signaling in B cells and dendritic cells for germinal center anti-nuclear antibody production in Lyn-deficient mice. J Immunol. 2014;192:875-85 pubmed publisher
    ..production in mice lacking MyD88 in B cells or DCs was accompanied by a dramatic decrease in the spontaneous germinal center (GC) response, suggesting that autoantibodies in Lyn(-/-) mice may depend on GC responses...
  37. Sagardoy A, Martínez Ferrandis J, Roa S, Bunting K, Aznar M, Elemento O, et al. Downregulation of FOXP1 is required during germinal center B-cell function. Blood. 2013;121:4311-20 pubmed publisher
    B-cell maturation and germinal center (GC) formation are dependent on the interplay between BCL6 and other transcriptional regulators...
  38. Barnett L, Simkins H, Barnett B, Korn L, Johnson A, Wherry E, et al. B cell antigen presentation in the initiation of follicular helper T cell and germinal center differentiation. J Immunol. 2014;192:3607-17 pubmed publisher
    High-affinity class-switched Abs and memory B cells are products of the germinal center (GC)...
  39. Peperzak V, Vikstrom I, Tarlinton D. Through a glass less darkly: apoptosis and the germinal center response to antigen. Immunol Rev. 2012;247:93-106 pubmed publisher
    ..and also for the normal expansion, contraction, and persistence of plasma cells, both extrafollicular and germinal center-derived...
  40. Silva J, Andrade A, Santana C, Santos L, Oliveira C, Veras P, et al. Low CXCL13 expression, splenic lymphoid tissue atrophy and germinal center disruption in severe canine visceral leishmaniasis. PLoS ONE. 2012;7:e29103 pubmed publisher
    ..is associated with the impairment of follicular dendritic cells, CXCL13 expression, B cell migration and germinal center formation and associates these changes with severe clinical forms of visceral leishmaniasis...
  41. Kim J, Kim D, Chang W, Choe J, Kim J, Park C, et al. Wnt5a is secreted by follicular dendritic cells to protect germinal center B cells via Wnt/Ca2+/NFAT/NF-?B-B cell lymphoma 6 signaling. J Immunol. 2012;188:182-9 pubmed publisher
    Follicular dendritic cells (FDCs) protect germinal center (GC) B cells from rapid apoptosis to allow their survival and maturation. In this article, we show that FDCs normally produce and secrete Wnt5a to protect GC B cells...
  42. Chang P, Barral P, Fitch J, Pratama A, Ma C, Kallies A, et al. Identification of Bcl-6-dependent follicular helper NKT cells that provide cognate help for B cell responses. Nat Immunol. 2011;13:35-43 pubmed publisher
    ..Unlike T cell-dependent germinal centers, those driven by NKT(FH) cells did not generate long-lived plasma cells. Our results demonstrate the existence of a Bcl-6-dependent subset of NKT cells specialized in providing help to B cells...
  43. Leich E, Zamo A, Horn H, Haralambieva E, Puppe B, Gascoyne R, et al. MicroRNA profiles of t(14;18)-negative follicular lymphoma support a late germinal center B-cell phenotype. Blood. 2011;118:5550-8 pubmed publisher
    ..expression in t(14;18)-negative FLs, whereas TCL1A expression was reduced, in line with a partial loss of the germinal center B-cell phenotype in this FL subset...
  44. Ma C, Deenick E, Batten M, Tangye S. The origins, function, and regulation of T follicular helper cells. J Exp Med. 2012;209:1241-53 pubmed publisher
  45. Basso K, Dalla Favera R. Roles of BCL6 in normal and transformed germinal center B cells. Immunol Rev. 2012;247:172-83 pubmed publisher
    BCL6 is a transcriptional repressor required in mature B cells during the germinal center (GC) reaction. Multiple mechanisms act coordinately to timely modulate BCL6 expression at transcriptional and post-transcriptional levels...
  46. De Silva N, Simonetti G, Heise N, Klein U. The diverse roles of IRF4 in late germinal center B-cell differentiation. Immunol Rev. 2012;247:73-92 pubmed publisher
    ..Within the B-cell lineage, IRF4 is expressed in all developmental stages except during the germinal center (GC) reaction...
  47. Kroenke M, Eto D, Locci M, Cho M, Davidson T, Haddad E, et al. Bcl6 and Maf cooperate to instruct human follicular helper CD4 T cell differentiation. J Immunol. 2012;188:3734-44 pubmed publisher
    ..Altogether, these findings reveal that Bcl6 and Maf collaborate to orchestrate a suite of genes that define core characteristics of human Tfh cell biology. ..
  48. Xu S, Guo K, Zeng Q, Huo J, Lam K. The RNase III enzyme Dicer is essential for germinal center B-cell formation. Blood. 2012;119:767-76 pubmed publisher
    ..More importantly, germinal center (GC) B-cell formation is drastically compromised in the absence of Dicer, as a result of defects in cell ..
  49. Wang X, Cho B, Suzuki K, Xu Y, Green J, An J, et al. Follicular dendritic cells help establish follicle identity and promote B cell retention in germinal centers. J Exp Med. 2011;208:2497-510 pubmed publisher
    ..These experiments indicate that FDCs help maintain primary follicles as a B cell exclusive niche and define a critical role for FDCs in cell retention within GCs...
  50. Li S, Lin P, Fayad L, Lennon P, Miranda R, Yin C, et al. B-cell lymphomas with MYC/8q24 rearrangements and IGH@BCL2/t(14;18)(q32;q21): an aggressive disease with heterogeneous histology, germinal center B-cell immunophenotype and poor outcome. Mod Pathol. 2012;25:145-56 pubmed publisher
    ..Of 48 cases assessed, 47 (98%) had a germinal center B-cell immunophenotype...
  51. Linterman M, Pierson W, Lee S, Kallies A, Kawamoto S, Rayner T, et al. Foxp3+ follicular regulatory T cells control the germinal center response. Nat Med. 2011;17:975-82 pubmed publisher
    Follicular helper (T(FH)) cells provide crucial signals to germinal center B cells undergoing somatic hypermutation and selection that results in affinity maturation. Tight control of T(FH) numbers maintains self tolerance...
  52. Maine C, Marquardt K, Cheung J, Sherman L. PTPN22 controls the germinal center by influencing the numbers and activity of T follicular helper cells. J Immunol. 2014;192:1415-24 pubmed publisher
    ..and in mice expressing the mouse homolog of the pro-autoimmune allele, PEP(R619W), have reported increased germinal center activity and enhanced Ab production...
  53. Leonard S, Wei W, Anderton J, Vockerodt M, Rowe M, Murray P, et al. Epigenetic and transcriptional changes which follow Epstein-Barr virus infection of germinal center B cells and their relevance to the pathogenesis of Hodgkin's lymphoma. J Virol. 2011;85:9568-77 pubmed publisher
    ..EBV) usually establishes an asymptomatic lifelong infection, it is also implicated in the development of germinal center (GC) B-cell-derived malignancies, including Hodgkin's lymphoma (HL)...