EXPRESSION OF THE IG-ALPHA AND IG-BETA MO LECULES IN HUMAN PRO-B CELL-LINES

Ig alpha and Ig beta are two glycosylated transmembrane proteins of th e Ig superfamily that are encoded by the B cell-specific genes mb-1 an d B29, respectively. Ig alpha/Ig beta heterodimers may associate with the mu l surrogate fight chains (Psi LC) complex and with membrane Imm unoglobulins on the surface of pre-B and B cells, respectively. They p lay a crucial role in the signal transduction that follows pre-B and B cell receptor cross-linking. Previous works have shown that mb-1 and B29 transcripts are expressed in normal mouse and human pro-B cells Ho wever, little is known about the expression of Ig alpha and Ig beta mo lecules in pro-B cells. Tb address this issue we first analysed the ex pression of the Ig alpha and Ig beta molecules in the RS4; 11 and Nalm 16 human pro-B cell lines using specific monoclonal antibodies We foun d that both cell lines expressed Ig alpha and Ig beta but this express ion was limited to the cytoplasm compartment. Three forms (44, 40 cmd 36 kDa) of the Ig alpha molecule and a single form (36 kDa) of the Ig beta molecule were detected in these lines. The heterogeneity of the I g alpha molecule was partly related to the presence of a truncated Ig alpha protein which is likely the product of a short mb-1 transcript e xpressed in these cell fines. This short transcript is generated by al ternative splicing of the mb1 mRNA with loss of exon 2. Ig alpha heter ogeneity was also related to the expression of different glycosylated forms of the Ig alpha molecule. Only a minor fraction of the Ig alpha and Ig beta molecules associate with each other to form Ig alpha/Ig be ta heterodimers and Ig beta homodimers. In these pro-B cell lines Ig a lpha and Ig beta were found to associate with the lyn tyrosine kinase, suggesting that they may play some functional role at this B cell dif ferentiation stage. Transfection of mu HC gene in the Nalm16 cells res ults in the assembly of the pre-B receptor and in its expression on th e cell surface. The level of surface expression of the pre-B receptor was found to correlate with the level of mu HC and Psi LC synthesis an d with the level of association of the different components of the pre -B receptor with each other. Analysis of the 697 and Nalm6 pre-B cells and of the Ramos B cells indicated that heterogeneity af Ig alpha and Ig beta increases as afunction of B cell differentiation.