Tyrosine phosphorylation is required for ligand-induced internalization of the antigen receptor on B lymphocytes.
The membrane immunoglobulin (mIg) receptor for antigen mediates signal transduction in B lymphocytes. Multivalent ligand induces several early activation events including an increase in intracellular calcium concentration, hydrolysis of phosphatidylinositol, and activation of protein kinase C. Most recently, it has been demonstrated that anti-immunoglobulin antibodies induce the rapid accumulation of tyrosine phosphorylated proteins and anti-phosphotyrosine immune complex-associated kinase activity, both of which require receptor crosslinking. Multivalent ligand binding of mIg also results in its association with detergent-insoluble cytoskeletal components and with a slight lag period, in a characteristic pattern of patching, followed by polar capping and finally internalization of the receptors. In this report, we demonstrate that two specific inhibitors of tyrosine phosphorylation, a tyrphostin and genistein, retard the modulation of mIg on the cell surface and inhibit ligand-induced receptor internalization. We conclude that in B cells, tyrosine phosphorylation occurs as the result of crosslinking mIg and is required for subsequent internalization of mIg-ligand complexes. This suggests that tyrosine phosphorylation may be important for B cells to function as specific antigen presenting cells.
Laboratory of Cellular Physiology and Immunology, Rockefeller University, New York, NY 10021.
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D000818:Animals; D000938:Antigen-Presenting Cells / Q000502:physiology; D001402:B-Lymphocytes / Q000378:metabolism*; D015536:Down-Regulation; D004705:Endocytosis; D005260:Female; D007072:Immunoglobulin D / Q000378:metabolism; D007075:Immunoglobulin M / Q000378:metabolism; D008024:Ligands; D008213:Lymphocyte Activation; D051379:Mice; D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism
D007072:Immunoglobulin D; D007075:Immunoglobulin M; D008024:Ligands; D011947:Receptors, Antigen, B-Cell; D019000:Phosphotyrosine; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases