MEMBRANE ISOFORMS OF HUMAN-IMMUNOGLOBULINS OF THE A1 AND A2 ISOTYPES - STRUCTURAL AND FUNCTIONAL-STUDY

As for IgM, human IgA occurs either as soluble molecules in plasma and various other body fluids, or as membrane-bound molecules on differen tiated B cells, where they are part of the B-cell receptor for antigen (BCR). We studied the structure of transcripts encoding the membrane- anchored alpha-chain of the human BGR alpha, which may be present in t wo different forms resulting from alternate splicing of the alpha-chai n mRNA (type I or type II). The ratio of type I versus type II did not vary upon stimulation of a B-cell line with various cytokines. Rather , it differed strikingly in cells expressing either the IgA1 or IgA2 i sotype of the BCR alpha, with virtually no type II a-chain in the latt er. Co-modulation experiments also yielded different results for both isotypes, since they demonstrated a physical association of both membr ane (m)IgA1 and mIgA2 with CD79b, the beta component of the BCR Ig alp ha/Ig beta heterodimer, but only of mIgA1 with CD19. Whatever the isot ype, the BCR of the IgA class was able to carry out signal transductio n upon cross-linking by specific monoclonal antibodies but, in contras t to mIgM, it relied mainly on the entry of extracellular Ca2+ rather than on the release of intracellular stocks.