Crosslinking of surface immunoglobulin and Fc receptors on B lymphocytes inhibits stimulation of inositol phospholipid breakdown via the antigen receptors.
F(ab')2 fragments of rabbit anti-mouse Ig induce proliferation of murine B lymphocytes, whereas the intact antibodies are not mitogenic. F(ab')2 anti-Ig stimulates the rapid breakdown of inositol phospholipids in B cells, resulting in the prolonged release of inositol (poly)phosphates and diacylglycerol. In marked contrast, intact anti-Ig initially induces a comparable response, which is abrogated after some 30 s. Blocking either the Fc receptors on the B cells or the Fc portion of the antibodies significantly reversed the inhibitory effect. On the other hand, both forms of anti-Ig elicited comparable increases in free cytoplasmic Ca2+ levels in B cells. These results therefore indicate that crosslinkage of Fc and surface Ig receptors on B cells inhibits inositol phospholipid breakdown (but not Ca2+ flux) resulting from ligation of the antigen receptors. Since there is evidence implicating inositol phospholipid breakdown in the induction of cell growth, this effect could provide a biochemical explanation for the known capacity of antigen-antibody complexes to inhibit B cell activation.
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000502:physiology*; D001402:B-Lymphocytes / Q000378:metabolism*; D001667:Binding, Competitive; D002118:Calcium / Q000378:metabolism; D003432:Cross-Linking Reagents; D003593:Cytoplasm / Q000378:metabolism; D007140:Immunoglobulin Fab Fragments / Q000276:immunology / Q000502:physiology; D015544:Inositol 1,4,5-Trisphosphate; D007295:Inositol Phosphates / Q000378:metabolism*; D008297:Male; D051379:Mice; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism / Q000502:physiology*; D011961:Receptors, Fc / Q000378:metabolism / Q000502:physiology*; D013205:Staphylococcal Protein A / Q000494:pharmacology; D013403:Sugar Phosphates / Q000378:metabolism*
D000888:Antibodies, Anti-Idiotypic; D003432:Cross-Linking Reagents; D007140:Immunoglobulin Fab Fragments; D007295:Inositol Phosphates; D011947:Receptors, Antigen, B-Cell; D011961:Receptors, Fc; D013205:Staphylococcal Protein A; D013403:Sugar Phosphates; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium