Modifications of Igα and Igβ expression as a function of B lineage differentiation

Abstract

Transcription of the mb1 and B29 genes is initiated when lymphoid progenitors enter the B cell differentiation pathway, and their transmembrane Igα and Igβ products constitute essential signaling components of pre-B and B cell antigen receptors. We analyzed Igα/Igβ 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 Igβ form and three principal Igα forms, transient 33/40-kDa species and a mature 44-kDa glycoprotein. Deglycosylation revealed a major Igα core protein of 25 kDa and a minor 21- kDa Igα protein, apparently the product of an alternatively spliced mRNA. In pro-B cells, the Igα and Igβ 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 Igα/Igβ molecules in pro-B cells. Greater heterogeneity of the Igα and Igβ molecules in pre-B and B cell lines was attributable to increased glycosylation complexity. Finally, the Igα/Igβ heterodimers associated with fully assembled IgM molecules as a terminal event in B cell receptor assembly.