Cluster of differentiation CD79A also known asB-cell antigen receptor complex-associated protein alpha chain andMB-1 membrane glycoprotein, is aprotein that in humans is encoded by the CD79Agene.[5]
The CD79a protein together with the relatedCD79b protein, forms adimer associated with membrane-boundimmunoglobulin inB-cells, thus forming theB-cell antigen receptor (BCR). This occurs in a similar manner to the association ofCD3 with theT-cell receptor, and enables the cell to respond to the presence ofantigens on its surface.[6]
The mouse CD79A gene, then called mb-1, was cloned in the late 1980s,[8] followed by the discovery of human CD79A in the early 1990s.[9][10] It is a short gene, 4.3 kb in length, with 5 exons encoding for 2 splice variants resulting in 2 isoforms.[5]
CD79A is conserved and abundant among ray-finned fish (actinopterygii) but not in the evolutionarily more ancientchondrichthyes such as shark.[11] The occurrence of CD79A thus coincides with the evolution of B cell receptors with greater diversity generated by recombination of multiple V, D, and J elements in bony fish contrasting the single V, D and J elements found in shark.[12]
CD79a is a membrane protein with an extracellular immunoglobulin domain, a single span transmembrane region and a short cytoplasmic domain.[5] The cytoplasmic domain contains multiple phosphorylation sites including a conserved dual phosphotyrosine binding motif, termed immunotyrosine-based activation motif (ITAM).[13][14] The larger CD79a isoform contains an insert in position 88-127 of human CD79a resulting in a complete immunoglobulin domain, whereas the smaller isoform has only a truncated Ig-like domain.[5] CD79a has severalcysteine residues, one of which forms covalent bonds with CD79b.[15]
CD79a plays multiple and diverse roles inB cell development and function. The CD79a/b heterodimer associates non-covalently with the immunoglobulin heavy chain through its transmembrane region, thus forming the BCR along with the immunoglobulin light chain and the pre-BCR when associated with the surrogate light chain in developing B cells. Association of the CD79a/b heterodimer with the immunoglobulin heavy chain is required for surface expression of the BCR and BCR induced calcium flux and protein tyrosine phosphorylation.[16] Genetic deletion of the transmembrane exon of CD79A results in loss of CD79a protein and a complete block of B cell development at the pro to pre B cell transition.[17] Similarly, humans with homozygous splice variants in CD79A predicted to result in loss of the transmembrane region and a truncated or absent protein display agammaglobulinemia and no peripheral B cells.[7][18][19]
The CD79aITAM tyrosines (human CD79a Tyr188 and Tyr199, mouse CD79a Tyr182 and Tyr193) phosphorylated in response to BCR crosslinking are critical for binding of Src-homology 2 domain-containing kinases such asspleen tyrosine kinase (Syk) and signal transduction by CD79a.[20][21] In vivo, the CD79aITAM tyrosines synergize with the CD79b ITAM tyrosines to mediate the transition from the pro to the pre B cell stage as suggested by the analysis of mice with targeted mutations of the CD79a and CD79bITAM.[22][23] Loss of only one of the two functional CD79a/b ITAMs resulted in impaired B cell development but B cell functions such as the T cell independent type II response and BCR mediated calcium flux in the available B cells were intact. However, the presence of both the CD79a and CD79bITAM tyrosines were required for normal T cell dependent antibody responses.[22][24] The CD79a cytoplasmic domain further contains a non-ITAM tyrosine distal to the CD79a ITAM (human CD79a Tyr210, mouse CD79a Tyr204) that can bind BLNK and Nck once phosphorylated,[25][26][27] and is critical for BCR mediated B cell proliferation and B1 cell development.[28] CD79aITAM tyrosine phosphorylation and signaling is negatively regulated by serine and threonine residues in direct proximity of the ITAM (human CD79a Ser197, Ser203, Thr209; mouse CD79a Ser191, Ser197, Thr203),[29][30] and play a role in limiting formation of bone marrow plasma cells secretingIgG2a andIgG2b.[23]
The CD79a protein is present on the surface of B-cells throughout their life cycle, and is absent on all other healthy cells, making it a highly reliable marker for B-cells inimmunohistochemistry. The protein remains present when B-cells transform into activeplasma cells, and is also present in virtually all B-cellneoplasms, including B-celllymphomas,plasmacytomas, andmyelomas. It is also present in abnormal lymphocytes associated with some cases ofHodgkins disease. Because even on B-cell precursors, it can be used to stain a wider range of cells than can the alternative B-cell markerCD20, but the latter is more commonly retained on mature B-cell lymphomas, so that the two are often used together in immunohistochemistry panels.[6]
^Flaswinkel H, Reth M (1992). "Molecular cloning of the Ig-alpha subunit of the human B-cell antigen receptor complex".Immunogenetics.36 (4):266–269.doi:10.1007/bf00215058.PMID1639443.S2CID28622219.
^Wang Y, Kanegane H, Sanal O, Tezcan I, Ersoy F, Futatani T, et al. (April 2002). "Novel Igalpha (CD79a) gene mutation in a Turkish patient with B cell-deficient agammaglobulinemia".American Journal of Medical Genetics.108 (4):333–336.doi:10.1002/ajmg.10296.PMID11920841.
^Reth M, Wienands J (1997). "Initiation and processing of signals from the B cell antigen receptor".Annual Review of Immunology.15 (1):453–479.doi:10.1146/annurev.immunol.15.1.453.PMID9143696.
^Castello A, Gaya M, Tucholski J, Oellerich T, Lu KH, Tafuri A, et al. (September 2013). "Nck-mediated recruitment of BCAP to the BCR regulates the PI(3)K-Akt pathway in B cells".Nature Immunology.14 (9):966–975.doi:10.1038/ni.2685.PMID23913047.S2CID2532325.
Müller B, Cooper L, Terhorst C (June 1992). "Cloning and sequencing of the cDNA encoding the human homologue of the murine immunoglobulin-associated protein B29".European Journal of Immunology.22 (6):1621–1625.doi:10.1002/eji.1830220641.PMID1534761.S2CID23910309.
Lankester AC, van Schijndel GM, Cordell JL, van Noesel CJ, van Lier RA (April 1994). "CD5 is associated with the human B cell antigen receptor complex".European Journal of Immunology.24 (4):812–816.doi:10.1002/eji.1830240406.PMID7512031.S2CID25093082.
Vasile S, Coligan JE, Yoshida M, Seon BK (April 1994). "Isolation and chemical characterization of the human B29 and mb-1 proteins of the B cell antigen receptor complex".Molecular Immunology.31 (6):419–427.doi:10.1016/0161-5890(94)90061-2.PMID7514267.
