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 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.
Leduc
I
I
Laboratoire d'Immunologie et Immunogénétique, CNRS EP 118, Faculté de Médecine, Limoges, France.
Drouet
M
M
Bodinier
M C
MC
Helal
A
A
Cogné
M
M
D017398:Alternative Splicing; D015703:Antigens, CD / Q000276:immunology; D018941:Antigens, CD19 / Q000276:immunology; D051925:CD79 Antigens; D002460:Cell Line; D002462:Cell Membrane / Q000276:immunology; D006801:Humans; D007070:Immunoglobulin A / Q000235:genetics* / Q000276:immunology*; D007378:Interleukins / Q000276:immunology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D011947:Receptors, Antigen, B-Cell / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology
D015703:Antigens, CD; D018941:Antigens, CD19; D051925:CD79 Antigens; C497883:CD79B protein, human; D007070:Immunoglobulin A; D007378:Interleukins; D012333:RNA, Messenger; D011947:Receptors, Antigen, B-Cell