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Membrane isoforms of human immunoglobulins of the A1 and A2 isotypes: structural and functional study
I Leduc1, M Drouet, M C Bodinier
1Laboratoire d'Immunologie et Immunogénétique, CNRS EP 118, Faculté de Médecine, Limoges, France.
As for IgM, human IgA occurs either as soluble molecules in plasma and various other body fluids, or as membrane-bound molecules on differentiated 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 BCR alpha, which may be present in two different forms resulting from alternate splicing of the alpha-chain 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 isotype of the BCR alpha, with virtually no type II alpha-chain in the latter. Co-modulation experiments also yielded different results for both isotypes, since they demonstrated a physical association of both membrane (m)IgA1 and mIgA2 with CD79b, the beta component of the BCR Ig alpha/Ig beta heterodimer, but only of mIgA1 with CD19. Whatever the isotype, the BCR of the IgA class was able to carry out signal transduction upon cross-linking by specific monoclonal antibodies but, in contrast to mIgM, it relied mainly on the entry of extracellular Ca2+ rather than on the release of intracellular stocks.
As for IgM, human IgA occurs either as soluble molecules in plasma and various other body fluids, or as membrane-bound molecules on differentiated 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 BCR alpha, which may be present in two different forms resulting from alternate splicing of the alpha-chain 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 isotype of the BCR alpha, with virtually no type II alpha-chain in the latter. Co-modulation experiments also yielded different results for both isotypes, since they demonstrated a physical association of both membrane (m)IgA1 and mIgA2 with CD79b, the beta component of the BCR Ig alpha/Ig beta heterodimer, but only of mIgA1 with CD19. Whatever the isotype, the BCR of the IgA class was able to carry out signal transduction upon cross-linking by specific monoclonal antibodies but, in contrast to mIgM, it relied mainly on the entry of extracellular Ca2+ rather than on the release of intracellular stocks.