Disease relevance of CD79A

• Human alpha heavy chain disease (HCD) is characterized by the presence in patient's serum of a short Ig alpha chain devoid of light chains [1].
• Normal lymphocytes as well as lymphoma cells of all non-Hodgkin's lymphomas tested were positive for leukocyte common antigen (LCA), and at variable degree, for MB 1, 4 KB 5, LN 1, LN 2, UCHL 1, or MT 1 [2].
• This mutant is expressed on the surface at high levels when transfected into a plasmacytoma line that lacks Ig alpha, whereas wild-type mu is retained in this cell line in the endoplasmic reticulum [3].
• The biodistribution, toxicity, and therapeutic potential of anti-CD37 monoclonal antibody (MoAb) MB-1 labeled with iodine 131 (131I) was evaluated in ten patients with advanced-, low- or intermediate-grade non-Hodgkin's lymphomas who failed conventional treatment [4].
• Treatment of refractory non-Hodgkin's lymphoma with radiolabeled MB-1 (anti-CD37) antibody [4].

High impact information on CD79A

• We assessed the biodistribution, toxicity, and efficacy of anti-CD20 (B1 and 1F5) and anti-CD37 (MB-1) antibodies labeled with iodine-131 in 43 patients with B-cell lymphoma in relapse [5].
• The Ig-alpha and Ig-beta proteins form a disulphide-linked alpha/beta heterodimer and are encoded by the mb-1 (ref 9, 10) and B29 genes, respectively [6].
• Both receptor types from a complex with the Ig alpha and Ig beta proteins that link the predominantly extracellular Ig with intracellular signal transduction pathways [7].
• In addition, we demonstrate that both ZAP-70 and Syk can bind directly to the phosphorylated Ig alpha and Ig beta subunits with affinities comparable to their binding to the TCR CD3 epsilon subunit [8].
• These findings not only confirm that both SH2 domains are necessary for Syk binding to tyrosine-phosphorylated Ig alpha and Ig beta but indicate that this binding is necessary for Syk (Y518/519) phosphorylation after BCR ligation [9].

Biological context of CD79A

• The predicted amino acid sequence was compared to its murine counterpart, to MB-1 and to the human T cell receptor (TcR)-associated CD3 proteins [10].
• Tyrosine phosphorylation of MB-1, B29, and HS1 proteins in human B cells following receptor crosslinking [11].
• Furthermore, we demonstrated that Ig alpha protein increases the access percentage of S phase from the early mitosis of synchronized cancer cells [12].
• The germline DNA sequence of the human CD79 alpha (Ig-alpha/mb-1) gene was determined by polymerase chain reaction sequencing of a cosmid clone derived from an arrayed human chromosome 19 library [13].
• We have defined variant RNA transcripts for both CD79a (Ig-alpha/mb-1) and CD79b (Ig-beta/B29) which appear to arise by alternative splicing [14].

Anatomical context of CD79A

• Since IgA is the key immunoglobulin which contributes to local immunity of mucous membrane, the aberrant expression of Ig alpha heavy chain might increase our further comprehension to development and immunity of cancers [15].
• Interestingly, our previous work demonstrated that epithelial cancer tissues and cancer cell lines also express Ig alpha heavy chain [12].
• To elucidate interactions occurring between B cell protein tyrosine kinases and the signaling components of the B cell antigen receptor, we have co-transfected into COS cells individual tyrosine kinases together with chimeric cell surface receptors containing the cytoplasmic domains of Ig alpha or Ig beta [16].
• We conclude that association of the four components, Ig-heavy chain (HC) and -light chain (LC), MB-1 and B29, is required and sufficient to permit exit of the BCR complex out of the endoplasmic reticulum (ER) [17].
• The MB-1-B29 heterodimer is required for deposition of the BCR at the plasma membrane, as well as for coupling of the antigen receptor to intracellular signal transduction cascades [17].

Associations of CD79A with chemical compounds

• The proteins encoded by these variants are predicted to conserve transmembrane and cytoplasmic portions of Ig-alpha and Ig-beta but lack a part of the extracellular portions containing cysteine residues which are required for intramolecular and intermolecular S-S bonds [18].
• A 32 kDa glycoprotein was identified, which is serologically related to MB-1, but has a more acidic isoelectric point (pl) and a protein backbone of 21 kDa, as compared with 25 kDa for MB-1 [17].
• The serine and threonine residues in the Ig-alpha cytoplasmic tail negatively regulate immunoreceptor tyrosine-based activation motif-mediated signal transduction [19].
• Mutations within the NH2-terminal transmembrane domain of membrane immunoglobulin (Ig) M alters Ig alpha and Ig beta association and signal transduction [20].
• Our study with castanospermine also showed that calnexin is required for wildtype mIgD surface expression only if Ig-alpha beta is absent, while the latter alone can function to promote mIg folding, assembly, and transport [21].

Physical interactions of CD79A

• We demonstrate that surface psi L expression is considerably enhanced upon interleukin-7 stimulation and that the psi L complex is formed independently of the Ig alpha/Ig beta heterodimer [22].
• The BCR is a complex between membrane immunoglobulin and the Ig-alpha and Ig-beta heterodimer [23].

Enzymatic interactions of CD79A

• The interaction is mediated by the Src homology 2 domain of SLP-65 and the phosphorylated Ig-alpha tyrosine 204, which is located outside of the immunoreceptor tyrosine-based activation motif [24].
• The tandem SH2 domains of the ZAP-70 tyrosine kinase bound to phosphorylated Ig-beta but only weakly to Ig-alpha [25].
• Also the SHC-derived SH2 domain formed complexes with the tyrosine-phosphorylated Ig-alpha/beta heterodimer, while the C- and N-terminal SH2 domains of GTPase-activating protein displayed completely different binding preferences [25].
• MB-1 is also phosphorylated in immune complexes prepared with antibodies to PTK72, indicating that components of the IgM complex are associated with PTK72 [26].

Regulatory relationships of CD79A

• In the B cell receptor-negative immature B cell lines RS4;11, 380, and REH, Ig alpha and Ig beta were expressed exclusively in the cytoplasm and were not tyrosine phosphorylated after CD38 ligation [27].
• The Ig-alpha and Ig-beta chimeras are each capable of inducing all of the BCR signaling events tested and thus represent redundant functions [23].

Other interactions of CD79A

• IgM, CD22, Ig-alpha, Ig-beta, and Syk were coimmunoprecipitated with CD19 from detergent lysates of B lymphocytes [28].
• In the present study, we investigated whether the cell surface membrane molecules used in B cell receptor-mediated signaling, such as Ig alpha, Ig beta, and CD19, could be involved in the CD38-mediated signaling cascade [27].
• The B cell antigen receptor, mIg, is part of a multimolecular complex including Ig alpha, Ig beta, and CD19 [29].
• Here we show that following B cell stimulation, SLP-65 associates directly with the BCR signaling subunit, the Ig-alpha / Ig-beta heterodimer [24].
• Requirements for selective recruitment of Ets proteins and activation of mb-1/Ig-alpha gene transcription by Pax-5 (BSAP) [30].

Analytical, diagnostic and therapeutic context of CD79A

• Molecular cloning of the Ig-alpha subunit of the human B-cell antigen receptor complex [31].
• This might open the possibility of removing MB-1-positive malignant cells from the graft in autologous bone marrow transplantation [32].
• Using four-color flow cytometry, we focused on the assessment of the CD79a antigen, which is highly B-cell specific and which may also be expressed very early in B-cell ontogeny [33].
• PURPOSE: This study was undertaken to evaluate the tumor targeting, toxicity, and therapeutic potential of the anti-B-cell-reactive monoclonal antibody MB-1 (anti-CD37) labeled with iodine 131 given in a nonmarrow ablative dose range in B-cell lymphoma patients who relapsed after chemotherapy [34].
• Ag binding to the membrane Ig (mIg) substructure of the B cell Ag receptor leads to activation of cytoplasmic effector molecules including blk, fyn, lyn, and/or lck tyrosine kinases that are associated with receptor's dimeric Ig-alpha/Ig-beta transducer substructure [35].

References