Modifications of Ig alpha and Ig beta expression as a function of B lineage differentiation

Transcription of the mb1 and B29 genes is initiated when lymphoid progenitors enter the B cell differentiation pathway, and their transmembrane Ig alpha and Ig beta products constitute essential signaling components of pre B and B cell antigen receptors. We analyzed Ig alpha/Ig beta biosynthesis, heterogeneity, and molecular interactions as a function of human B lineage differentiation in cell lines representative of the pro-B, pre-B, and B cell stages. All B lineage representatives produced a 36-kDa Ig beta form and three principal Ig alpha forms, transient 33/40-kDa species and a mature 44-kDa glycoprotein. Deglycosylation revealed a major Ig alpha core protein of 25 kDa and a minor 21-kDa Ig alpha protein, apparently the product of an alternatively spliced mRNA. In pro-B cells, the Ig alpha and Ig beta molecules existed primarily in separate unassembled pools, exhibited an immature glycosylation pattern, did not associate with surrogate Light chain proteins, and were retained intracellularly. Their unanticipated association with the Lyn protein-tyrosine kinase nevertheless suggests functional potential for the Ig alpha/Ig beta molecules in pro-B cells. Greater heterogeneity of the Iglu and Ig beta molecules in pre-B and B cell Lines was attributable to increased glycosylation complexity. Finally, the Ig alpha/Ig beta heterodimers associated with fully assembled IgM molecules as a terminal event in B cell receptor assembly.