Cloning and sequencing of the cDNA encoding the human homologue of the murine immunoglobulin‐associated protein B29

Abstract

Membrane-bound immunoglobulins (Ig) on the surface of murine B cells are noncovalently associated with a heterodimeric protein complex of MB-1 and B29 (also called Ig-alpha and Ig-beta). The Ig-associated proteins are predicted to regulate the assembly and transport of the Ig complex to the cell surface and to couple membrane-bound Ig to intracellular signal transduction pathways. We have isolated and sequenced a full-length cDNA clone encoding the human homologue of the B29 protein. 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. The alignment of the human B29 protein with its murine counterpart revealed 90% homology in the C-terminal portion comprising the cytoplasmic tails, the transmembrane regions and the adjacent 26 amino acids of the extracellular regions. Only 59% homology was found in the rest of the Ig-like extracellular domains. The high degree of conservation observed for the C-terminal amino acids suggested that these domains of the proteins play important functional roles for the Ig complex. Indicative of this was the conservation of the antigen receptor tail motif D-(X)7-E/D-(X)2-Y-(X)2-L-(X)7-Y-(X)2-L/I which is thought to be a component of signal transduction pathways. This motif is also found in the human and murine MB-1 proteins as well as in the TcR-associated CD3 molecules. Further regions of homology between B29, MB-1 and the CD3 proteins included extracellular residues which were predicted to maintain the Ig-like structure, and hydrophilic residues within the transmembrane regions which may be utilized during the intracellular assembly and transport of the oligomeric Ig/MB-1/B29 or TcR/CD3 complexes. Thus the similarities found between B29, MB-1 and the CD3 proteins suggest conserved functions for both the Ig- and TcR-associated proteins.

Modifications of Igα and Igβ Expression as a Function of B Lineage Differentiation

“…Antibodies to the C-terminal portion of Ig␤ are needed to determine whether this truncated Ig␤ is expressed in pro-B cells. The present RT-PCR and sequence analyses of pro-B cell lines thus agree with those previously reported for human pre-B and B cell lines (41)(42)(43)(44)(45). 2) and anti-Ig␤ mAbs (lanes 3 and 4).…”

The structure of the μ/pseudo light chain complex on human pre‐B cells is consistent with a function in signal transduction

“…Products of the B cell specific genes mb-1 [21-231 and B29 [24,25] form a disulfide-linked heterodimer and are non-covalently bound to mIgM in murine [26-281 and human [29-331 B cells. The mIg-associated heterodimer is believed to bind to H chains in the transmembrane region, forming a hydrophobic sheath around the polar amino acid residues that prevent surface expression of single H chain molecules [20].…”

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

“…The ITAM is a signaling molecule found in the receptors of T and B lymphocytes, as well as various other Fc receptor harboring cells in the vertebrate immune system [7, 8, 86]. The overall ITAM consensus is D/E(X) 7 D/E(X) 2 Y(X) 2 L/I(X) 6–8 Y(X) 2 L/I where X is any amino acids, Y is tyrosine, L and I are leucine and isoleucine residues and D and E are aspartic acid and glutamic acid residues [6, 12, 18].…”