Genomes and Genes
Gene Symbol: Ig alpha
Description: CD79A antigen (immunoglobulin-associated alpha)
Alias: Ig-alpha, Iga, Igalpha, Ly-54, Ly54, mb-1, B-cell antigen receptor complex-associated protein alpha chain, Ig alpha, MB-1 membrane glycoprotein, immunoglobulin-associated alpha, membrane-bound immunoglobulin-associated protein, surface IgM-associated protein
Products: Ig alpha
- Yabas M, Teh C, Frankenreiter S, Lal D, Roots C, Whittle B, et al. ATP11C is critical for the internalization of phosphatidylserine and differentiation of B lymphocytes. Nat Immunol. 2011;12:441-9 pubmed publisher..The only other abnormalities we noted were anemia, hyperbilirubinemia and hepatocellular carcinoma. Our results identify an intimate connection between phospholipid transport and B lymphocyte function. ..
- Kraus M, Alimzhanov M, Rajewsky N, Rajewsky K. Survival of resting mature B lymphocytes depends on BCR signaling via the Igalpha/beta heterodimer. Cell. 2004;117:787-800 pubmed..Kinetic data demonstrate that BCR-less mature B cells have a severely reduced lifespan, with a half-life of 3-6 days. Together these results establish that BCR signaling is required to keep resting mature B cells alive in vivo. ..
- Silva D, Daley S, Hogan J, Lee S, Teh C, Hu D, et al. Anti-islet autoantibodies trigger autoimmune diabetes in the presence of an increased frequency of islet-reactive CD4 T cells. Diabetes. 2011;60:2102-11 pubmed publisher..Cooperation between inherited variants affecting CD4 T-cell tolerance and anti-islet autoantibodies should be examined in epidemiological studies and in studies examining the efficacy of B-cell depletion. ..
- Torres R, Flaswinkel H, Reth M, Rajewsky K. Aberrant B cell development and immune response in mice with a compromised BCR complex. Science. 1996;272:1804-8 pubmed..B cells that do develop demonstrate a differential dependence on Ig-alpha signaling in antibody responses such that a signaling-competent Ig-alpha appears to be critical for the response to T-independent, but not T-dependent, antigens. ..
- Sakaguchi N, Kashiwamura S, Kimoto M, Thalmann P, Melchers F. B lymphocyte lineage-restricted expression of mb-1, a gene with CD3-like structural properties. EMBO J. 1988;7:3457-64 pubmed..Antibodies raised against a stretch of 20 amino acids of the putative intracellular domain with 90% homology between the mouse and human protein did not stain the surface of any cell lines tested.(ABSTRACT TRUNCATED AT 250 WORDS) ..
- Dengler H, Baracho G, Omori S, Bruckner S, Arden K, Castrillon D, et al. Distinct functions for the transcription factor Foxo1 at various stages of B cell differentiation. Nat Immunol. 2008;9:1388-98 pubmed publisher..Thus, Foxo1 regulates a transcriptional program that is essential for early B cell development and peripheral B cell function. ..
- Otipoby K, Sasaki Y, Schmidt Supprian M, Patke A, Gareus R, Pasparakis M, et al. BAFF activates Akt and Erk through BAFF-R in an IKK1-dependent manner in primary mouse B cells. Proc Natl Acad Sci U S A. 2008;105:12435-8 pubmed publisher..In combination with the known role of IKK1 in regulating transcription of prosurvival genes, our data underscore the central role of IKK1 in coordinating multiple BAFF-R-mediated signaling pathways controlling mature B cell homeostasis. ..
- Reichlin A, Gazumyan A, Nagaoka H, Kirsch K, Kraus M, Rajewsky K, et al. A B cell receptor with two Igalpha cytoplasmic domains supports development of mature but anergic B cells. J Exp Med. 2004;199:855-65 pubmed..b>Igalpha and Igbeta are redundant in their ability to support early B cell development, but their roles in mature B cells ..
- Sims R, Vandergon V, Malone C. The mouse B cell-specific mb-1 gene encodes an immunoreceptor tyrosine-based activation motif (ITAM) protein that may be evolutionarily conserved in diverse species by purifying selection. Mol Biol Rep. 2012;39:3185-96 pubmed publisher..In addition, an overall comparison of non-synonymous and synonymous nucleotide mutational changes suggests that the mb-1 gene has undergone purifying selection throughout its evolution. ..
- Patterson H, Kraus M, Kim Y, Ploegh H, Rajewsky K. The B cell receptor promotes B cell activation and proliferation through a non-ITAM tyrosine in the Igalpha cytoplasmic domain. Immunity. 2006;25:55-65 pubmedIn addition to the tyrosines of the Igalpha and beta immunoreceptor tyrosine-based activation motifs (ITAMs), the evolutionarily conserved Igalpha non-ITAM tyrosine 204 becomes phosphorylated upon antigen recognition by the B cell ..
- Torres R, Hafen K. A negative regulatory role for Ig-alpha during B cell development. Immunity. 1999;11:527-36 pubmed..These data illustrate a role for Ig-alpha in negatively regulating antigen receptor signaling during B cell development. ..
- Bain G, Maandag E, Izon D, Amsen D, Kruisbeek A, Weintraub B, et al. E2A proteins are required for proper B cell development and initiation of immunoglobulin gene rearrangements. Cell. 1994;79:885-92 pubmed..In addition, we show that Pax-5 transcripts are significantly reduced in fetal livers of E2A (-/-) mice. These data suggest a crucial role for E2A products as central regulators in early B cell differentiation. ..
- Kitaura Y, Jang I, Wang Y, Han Y, Inazu T, Cadera E, et al. Control of the B cell-intrinsic tolerance programs by ubiquitin ligases Cbl and Cbl-b. Immunity. 2007;26:567-78 pubmed..Thus, Cbl proteins control B cell-intrinsic checkpoint of immune tolerance, possibly through coordinating multiple BCR-proximal signaling pathways during anergy induction. ..
- Fuentes Panana E, Bannish G, Karnell F, Treml J, Monroe J. Analysis of the individual contributions of Igalpha (CD79a)- and Igbeta (CD79b)-mediated tonic signaling for bone marrow B cell development and peripheral B cell maturation. J Immunol. 2006;177:7913-22 pubmedThe individual contribution of Igalpha and Igbeta for BCR-triggered fates is unclear. Prior evidence supports conflicting ideas concerning unique as well as redundant functions for these proteins in the context of BCR/pre-BCR signaling...
- Gazumyan A, Reichlin A, Nussenzweig M. Ig beta tyrosine residues contribute to the control of B cell receptor signaling by regulating receptor internalization. J Exp Med. 2006;203:1785-94 pubmed..In addition, B cells with the ITAM mutant receptor showed an enhanced response to a T-independent antigen. Thus, Igbeta ITAM tyrosines help set BCR signaling threshold by regulating receptor internalization. ..
- Kabak S, Skaggs B, Gold M, Affolter M, West K, Foster M, et al. The direct recruitment of BLNK to immunoglobulin alpha couples the B-cell antigen receptor to distal signaling pathways. Mol Cell Biol. 2002;22:2524-35 pubmedFollowing B-cell antigen receptor (BCR) ligation, the cytoplasmic domains of immunoglobulin alpha (Ig alpha) and Ig beta recruit Syk to initiate signaling cascades...
- Clark M, Johnson S, Cambier J. Analysis of Ig-alpha-tyrosine kinase interaction reveals two levels of binding specificity and tyrosine phosphorylated Ig-alpha stimulation of Fyn activity. EMBO J. 1994;13:1911-9 pubmed
- Reichlin A, Hu Y, Meffre E, Nagaoka H, Gong S, Kraus M, et al. B cell development is arrested at the immature B cell stage in mice carrying a mutation in the cytoplasmic domain of immunoglobulin beta. J Exp Med. 2001;193:13-23 pubmed..cytoplasmic domain of Ig beta (Ig beta Delta C mice) and compared them to mice that carry a similar mutation in Ig alpha (MB1 Delta C, herein referred to as Ig alpha Delta C mice)...
- Patterson H, Kraus M, Wang D, Shahsafaei A, Henderson J, Seagal J, et al. Cytoplasmic Ig alpha serine/threonines fine-tune Ig alpha tyrosine phosphorylation and limit bone marrow plasma cell formation. J Immunol. 2011;187:2853-8 pubmed publisher..Our results suggest that Ig? serine/threonines limit formation of IgG2c- and IgG2b-secreting bone marrow plasma cells, possibly by fine-tuning Ig? tyrosine-mediated BCR signaling. ..
- Pelanda R, Hobeika E, Kurokawa T, Zhang Y, Kuppig S, Reth M. Cre recombinase-controlled expression of the mb-1 allele. Genesis. 2002;32:154-7 pubmed
- Rowland S, Depersis C, Torres R, Pelanda R. Ras activation of Erk restores impaired tonic BCR signaling and rescues immature B cell differentiation. J Exp Med. 2010;207:607-21 pubmed publisher..These results strongly suggest that tonic BCR signaling mediates the differentiation of immature into transitional and mature B cells via activation of Erk, likely through a pathway requiring Ras. ..
- Kraus M, Pao L, Reichlin A, Hu Y, Canono B, Cambier J, et al. Interference with immunoglobulin (Ig)alpha immunoreceptor tyrosine-based activation motif (ITAM) phosphorylation modulates or blocks B cell development, depending on the availability of an Igbeta cytoplasmic tail. J Exp Med. 2001;194:455-69 pubmed..Ig)alpha immunoreceptor tyrosine-based activation motif (ITAM) phosphorylation, we generated mice in which Igalpha ITAM tyrosines were replaced by phenylalanines (Igalpha(FF/FF))...
- Herzog S, Hug E, Meixlsperger S, Paik J, Depinho R, Reth M, et al. SLP-65 regulates immunoglobulin light chain gene recombination through the PI(3)K-PKB-Foxo pathway. Nat Immunol. 2008;9:623-31 pubmed publisher..Together, these data illuminate a molecular function of SLP-65 and identify a key role for Foxo proteins in the regulation of light chain recombination, receptor editing and B cell selection. ..
- O Neill S, Getahun A, Gauld S, Merrell K, Tamir I, Smith M, et al. Monophosphorylation of CD79a and CD79b ITAM motifs initiates a SHIP-1 phosphatase-mediated inhibitory signaling cascade required for B cell anergy. Immunity. 2011;35:746-56 pubmed publisher..Thus, chronic BCR signals maintain anergy in part via ITAM monophosphorylation-directed activation of an inhibitory signaling circuit involving SHIP-1 and Dok-1. ..
- Pelanda R, Braun U, Hobeika E, Nussenzweig M, Reth M. B cell progenitors are arrested in maturation but have intact VDJ recombination in the absence of Ig-alpha and Ig-beta. J Immunol. 2002;169:865-72 pubmed..Finally, Ig-alpha and Ig-beta are not redundant in their putative function, as pro-B cells from Ig-alpha and Ig-beta double-deficient mice are similar to those from single-deficient animals in every aspect analyzed. ..
- Daley S, Coakley K, Hu D, Randall K, Jenne C, Limnander A, et al. Rasgrp1 mutation increases naive T-cell CD44 expression and drives mTOR-dependent accumulation of Helios? T cells and autoantibodies. elife. 2013;2:e01020 pubmed publisher..DOI: http://dx.doi.org/10.7554/eLife.01020.001. ..
- Hombach J, Lottspeich F, Reth M. Identification of the genes encoding the IgM-alpha and Ig-beta components of the IgM antigen receptor complex by amino-terminal sequencing. Eur J Immunol. 1990;20:2795-9 pubmed
- Yamashita T, Inui S, Maeda K, Hua D, Takagi K, Sakaguchi N. The heterodimer of alpha4 and PP2Ac is associated with S6 kinase1 in B cells. Biochem Biophys Res Commun. 2005;330:439-45 pubmed..These results suggest that alpha4 regulates S6K1 activity through PP2Ac in B cell activation. ..
- Liu H, Schmidt Supprian M, Shi Y, Hobeika E, Barteneva N, Jumaa H, et al. Yin Yang 1 is a critical regulator of B-cell development. Genes Dev. 2007;21:1179-89 pubmed..We provide evidence that YY1 binds the intronic Ei mu enhancer within the IgH locus, consistent with a direct role for YY1 in V(H)D(H)J(H) recombination. These findings identified YY1 as a critical regulator of early B-cell development. ..
- Kim J, Lee S, Jeon Y, Kim Y, Lee C, Jeon S, et al. TopBP1 deficiency impairs V(D)J recombination during lymphocyte development. EMBO J. 2014;33:217-28 pubmed publisher..The developmental defects were rescued by introducing functional TCR ?? transgenes. Our data demonstrate a novel role for TopBP1 as a crucial factor in V(D)J rearrangement during the development of B, T and iNKT cells. ..
- Green M, Vicente Dueñas C, Romero Camarero I, Long Liu C, Dai B, González Herrero I, et al. Transient expression of Bcl6 is sufficient for oncogenic function and induction of mature B-cell lymphoma. Nat Commun. 2014;5:3904 pubmed publisher..Together, these results suggest that BCL6 may function in a 'hit-and-run' role in lymphomagenesis. ..
- Pasquarella A, Ebert A, Pereira de Almeida G, Hinterberger M, Kazerani M, Nuber A, et al. Retrotransposon derepression leads to activation of the unfolded protein response and apoptosis in pro-B cells. Development. 2016;143:1788-99 pubmed publisher..Production of MLV proteins leads to activation of the unfolded protein response pathway and apoptosis. Thus, our data demonstrate that B cell development depends on the proper repression of retrotransposon sequences through Setdb1. ..
- Verma Gaur J, Torkamani A, Schaffer L, Head S, Schork N, Feeney A. Noncoding transcription within the Igh distal V(H) region at PAIR elements affects the 3D structure of the Igh locus in pro-B cells. Proc Natl Acad Sci U S A. 2012;109:17004-9 pubmed publisher..Therefore, we hypothesize that one key role of noncoding germ-line transcription is to facilitate locus compaction, allowing distal V(H) genes to undergo efficient rearrangement. ..
- Feldman A, Tucker R, Fenner E, Pelanda R, Mack C. B cell deficient mice are protected from biliary obstruction in the rotavirus-induced mouse model of biliary atresia. PLoS ONE. 2013;8:e73644 pubmed publisher..The mechanism of protection may involve lack of B cell antigen presentation, which impairs T-cell activation and Th1 inflammation. Immune modulators that inhibit B cell function may be a new strategy for treatment of BA. ..
- Duque Afonso J, Lin C, Han K, Wei M, Feng J, Kurzer J, et al. E2A-PBX1 Remodels Oncogenic Signaling Networks in B-cell Precursor Acute Lymphoid Leukemia. Cancer Res. 2016;76:6937-6949 pubmed..Our results show how the oncogenic fusion protein E2A-PBX1 perturbs signaling pathways upstream of PLC?2 and renders leukemias amenable to targeted therapeutic inhibition. Cancer Res; 76(23); 6937-49. ©2016 AACR. ..
- Coffre M, Benhamou D, RieÃŸ D, Blumenberg L, Snetkova V, Hines M, et al. miRNAs Are Essential for the Regulation of the PI3K/AKT/FOXO Pathway and Receptor Editing during BÂ Cell Maturation. Cell Rep. 2016;17:2271-2285 pubmed publisher..Our analysis revealed that miRNAs are critical for the regulation of the PTEN-AKT-FOXO1 pathway that inÂ turn controls Rag expression during B cell development. ..
- Schüler F, Weiss J, Lindner S, Lohmüller M, Herzog S, Spiegl S, et al. Checkpoint kinase 1 is essential for normal B cell development and lymphomagenesis. Nat Commun. 2017;8:1697 pubmed publisher..Our findings define CHK1 as essential in B-cell development and potent target to treat blood cancer. ..
- Arnon T, Horton R, Grigorova I, Cyster J. Visualization of splenic marginal zone B-cell shuttling and follicular B-cell egress. Nature. 2013;493:684-8 pubmed publisher..The results also show how adhesive differences of similar cells critically influence their behaviour in the same microenvironment...
- Sitte S, Gläsner J, Jellusova J, Weisel F, Panattoni M, Pardi R, et al. JAB1 is essential for B cell development and germinal center formation and inversely regulates Fas ligand and Bcl6 expression. J Immunol. 2012;188:2677-86 pubmed publisher..These findings identify JAB1 as an important factor in checkpoint control during early B cell development, as well as in fate decisions in mature Ag-primed B cells. ..
- Pang S, Minnich M, Gangatirkar P, Zheng Z, Ebert A, Song G, et al. PU.1 cooperates with IRF4 and IRF8 to suppress pre-B-cell leukemia. Leukemia. 2016;30:1375-87 pubmed publisher..1/IRF4/IRF8, and restoration of Ikaros or Spi-B expression inhibited leukemic cell growth. In summary, we demonstrate that PU.1, IRF4 and IRF8 cooperate to regulate early B-cell development and to prevent pre-B-ALL formation. ..
- Schwickert T, Tagoh H, Gultekin S, Dakic A, Axelsson E, Minnich M, et al. Stage-specific control of early B cell development by the transcription factor Ikaros. Nat Immunol. 2014;15:283-93 pubmed publisher..Notably, binding of Ikaros and expression of its target genes were dynamically regulated at distinct stages of early B lymphopoiesis. ..
- Travis A, Hagman J, Grosschedl R. Heterogeneously initiated transcription from the pre-B- and B-cell-specific mb-1 promoter: analysis of the requirement for upstream factor-binding sites and initiation site sequences. Mol Cell Biol. 1991;11:5756-66 pubmed..From these data, we conclude that upstream factor-binding sites in the TATA-less mb-1 promoter define a region in which initiation of transcription occurs at multiple sites. ..
- Campbell K, Hager E, Friedrich R, Cambier J. IgM antigen receptor complex contains phosphoprotein products of B29 and mb-1 genes. Proc Natl Acad Sci U S A. 1991;88:3982-6 pubmed..The deduced sequence indicates that these receptor subunits lack inherent protein kinase domains but include common tyrosine-containing sequence motifs, which are likely sites of induced tyrosine phosphorylation. ..
- Mantis N, Cheung M, Chintalacharuvu K, Rey J, Corthesy B, Neutra M. Selective adherence of IgA to murine Peyer's patch M cells: evidence for a novel IgA receptor. J Immunol. 2002;169:1844-51 pubmed..In rodents and rabbits, Peyer's patch M cells selectively bind and endocytose secretory IgA (SIgA) Abs. Neither the nature of the M cell IgR nor the domains of SIgA involved in this interaction are known...
- Diaz MuÃ±oz M, Bell S, Fairfax K, Monzon Casanova E, Cunningham A, Gonzàlez Porta M, et al. The RNA-binding protein HuR is essential for the B cell antibody response. Nat Immunol. 2015;16:415-25 pubmed publisher..Our study shows how post-transcriptional processes control the balance of energy metabolism required for the proliferation and differentiation of B cells. ..
- Nolte M, Arens R, Kraus M, van Oers M, Kraal G, van Lier R, et al. B cells are crucial for both development and maintenance of the splenic marginal zone. J Immunol. 2004;172:3620-7 pubmed..mouse model in which mature B cells could be partially depleted by removal of the B cell receptor subunit Igalpha, we could show that the integrity and function of an established marginal zone was also dependent on the presence ..
- Kim J, Cramer L, Mueller H, Wilson B, Vilen B. Independent trafficking of Ig-alpha/Ig-beta and mu-heavy chain is facilitated by dissociation of the B cell antigen receptor complex. J Immunol. 2005;175:147-54 pubmed..In summary, we found that Ag stimulation physically separates Ig-alphabeta from mum, facilitating concomitant signal transduction and Ag delivery to the endocytic compartment. ..
- Laidlaw B, Schmidt T, Green J, Allen C, Okada T, Cyster J. The Eph-related tyrosine kinase ligand Ephrin-B1 marks germinal center and memory precursor B cells. J Exp Med. 2017;214:639-649 pubmed publisher..These findings offer insight into the significant heterogeneity that exists within the GC B cell population and provide tools to further dissect signals regulating the differentiation of GC B cells. ..
- Cheng P, Brown B, Song W, Pierce S. Translocation of the B cell antigen receptor into lipid rafts reveals a novel step in signaling. J Immunol. 2001;166:3693-701 pubmed..which the earliest events involve the phosphorylation of the immunoreceptor tyrosine-based activation motifs of Ig alpha and Ig beta by the Src family kinase Lyn and association of the BCR with the actin cytoskeleton...
- Luis T, Luc S, Mizukami T, Boukarabila H, Thongjuea S, Woll P, et al. Initial seeding of the embryonic thymus by immune-restricted lympho-myeloid progenitors. Nat Immunol. 2016;17:1424-1435 pubmed publisher..Moreover, studies of embryos deficient in the transcriptional regulator RBPJ demonstrated that canonical Notch signaling was not involved in pre-thymic restriction to the T cell lineage or the migration of T-IPs. ..
- Lee W, Tolar P. Activation of the B cell receptor leads to increased membrane proximity of the Ig? cytoplasmic domain. PLoS ONE. 2013;8:e79148 pubmed publisher..Thus, BCR activation is accompanied by asymmetric conformational changes, possibly promoting the binding of Ig? and Ig? to differently localized signaling complexes. ..
- Debnath I, Roundy K, Pioli P, Weis J, Weis J. Bone marrow-induced Mef2c deficiency delays B-cell development and alters the expression of key B-cell regulatory proteins. Int Immunol. 2013;25:99-115 pubmed publisher..Chromatin immunoprecipitation analysis confirmed Mef2c binding to the promoters of these genes indicating a direct link between the presence (or absence) of Mef2c and altered transcriptional control in mature B-cells. ..
- Giles A, Bender T, Ravichandran K. The adaptor protein Shc plays a key role during early B cell development. J Immunol. 2009;183:5468-76 pubmed publisher..Together, these data demonstrate a critical role for Shc in early B lymphopoiesis with a requirement in early B cell survival. In addition, we also identify Shc as a required player in signaling downstream of the IL-7R in early B cells. ..
- Sakurai N, Maeda M, Lee S, Ishikawa Y, Li M, Williams J, et al. The LRF transcription factor regulates mature B cell development and the germinal center response in mice. J Clin Invest. 2011;121:2583-98 pubmed publisher..These studies identify what we believe to be a new key factor for mature B cell development and provide a rationale for targeting LRF dimers for the treatment of autoimmune diseases and B cell malignancies. ..
- Lee S, Silva D, Martin J, Pratama A, Hu X, Chang P, et al. Interferon-? excess leads to pathogenic accumulation of follicular helper T cells and germinal centers. Immunity. 2012;37:880-92 pubmed publisher..This link between IFN-? and aberrant Tfh cell formation provides a rationale for IFN-? blockade in lupus patients with an overactive Tfh cell-associated pathway. ..
- Maier H, Colbert J, Fitzsimmons D, Clark D, Hagman J. Activation of the early B-cell-specific mb-1 (Ig-alpha) gene by Pax-5 is dependent on an unmethylated Ets binding site. Mol Cell Biol. 2003;23:1946-60 pubmed..Together, these studies demonstrate a novel DNA methylation-dependent mechanism for regulating transcriptional activity through the inhibition of DNA-dependent protein-protein interactions. ..
- Pore D, Matsui K, Parameswaran N, Gupta N. Cutting Edge: Ezrin Regulates Inflammation by Limiting B Cell IL-10 Production. J Immunol. 2016;196:558-62 pubmed publisher..Taken together, our data yield new insights into molecular and membrane-cytoskeletal regulation of B cell IL-10 production and reveal ezrin as a potential therapeutic target in inflammatory diseases. ..
- Nambu Y, Sugai M, Gonda H, Lee C, Katakai T, Agata Y, et al. Transcription-coupled events associating with immunoglobulin switch region chromatin. Science. 2003;302:2137-40 pubmed..These data indicate an important role of GLT in the regulation of chromatin accessibility, strongly suggesting that the target of AID is chromatin DNA. Our results give insights on the role of AID and the regulatory mechanism of CSR. ..
- Fuentes Panana E, Bannish G, Shah N, Monroe J. Basal Igalpha/Igbeta signals trigger the coordinated initiation of pre-B cell antigen receptor-dependent processes. J Immunol. 2004;173:1000-11 pubmed..can promote pre-BCR-dependent processes, we used a surrogate pre-BCR consisting of the cytoplasmic regions of Igalpha/Igbeta that is targeted to the inner leaflet of the plasma membrane of primary pro-B cells...