Fc receptor phosphorylation during receptor-mediated control of B-cell activation

Abstract

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 agents¹. 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^2,3. 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^2–6. This form of regulation may have a role in the induction of tolerance by IgG⁷ and in controlling the B-cell repertoire by anti-idiotypes^8,9. 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^10,11. 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.