Fc receptor phosphorylation during receptor-mediated control of B-cell activation.
It is well known that Fc receptors for IgG (FcRII) on macrophages mediate the endocytosis of antibody-antigen complexes and signal the release of inflammatory and cytotoxic agents. FcRII are also expressed at high levels on B cells where they are less involved in endocytosis than in modulating B-cell activation by membrane immunoglobulins. Although crosslinking of membrane immunoglobulins can result in B-cell differentiation and proliferation through stimulation of phospholipase C, mobilization of intracellular Ca2+, and activation of protein kinase C, crosslinking FcR with membrane immunoglobulins confers a dominant inhibitory signal that prevents or aborts activation. This form of regulation may have a role in the induction of tolerance by IgG and in controlling the B-cell repertoire by anti-idiotypes. The different functions of FcR on B cells and macrophages may reflect the fact that these cell types express closely related but distinct FcR isoforms. We have recently found that the main lymphocyte FcR isoform, FcRII-B1, is unable to mediate endocytosis by way of coated pits and coated vesicles owing to an in-frame insertion of 47 amino acids in its cytoplasmic tail. Here we show that this insert, absent from the FcRII-B2 macrophage isoform, also contains serine phosphorylation sites that may have a role in the ability of FcR to regulate B-cell activation through membrane immunoglobulins.
Department of Cell Biology, Yale University School of Medicine, New Haven, Connecticut 06510.
W
W
Hunziker
T
T
Koch
J A
JA
Whitney
I
I
Mellman
D000470:Alkaloids / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D002462:Cell Membrane / Q000276:immunology; D006224:Cricetinae; D003432:Cross-Linking Reagents; D004247:DNA / Q000235:genetics; D004285:Dogs; D007136:Immunoglobulins / Q000276:immunology; D007163:Immunosorbent Techniques; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D011961:Receptors, Fc / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014162:Transfection
D000470:Alkaloids; D003432:Cross-Linking Reagents; D007136:Immunoglobulins; D011961:Receptors, Fc; D004247:DNA; D011493:Protein Kinase C; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate