Developmentally regulated association of a 56-kD member of the surface immunoglobulin M receptor complex.
Immature and mature B cells differ in the signals generated and transduced through their antigen receptor, surface immunoglobulin M (sIgM). Whereas signals generated through sIgM on mature B cells initiate a program leading to the positive activation of these cells, signaling through this receptor at the immature stage of development leads to a state of induced unresponsiveness or tolerance. Our previous studies have described developmental differences in sIgM transmembrane signaling that are independent of ligand-receptor affinity. In an attempt to understand the molecular basis for signaling differences between immature and mature B cells, we have analyzed the sIgM receptor complex in neonatal and adult mouse splenic B cells. While previously described components of this complex do not exhibit marked developmentally regulated differences in their association with sIgM, we have identified a 56-kD protein that associates with sIgM in mature (antigen-responsive), but not immature (tolerance-sensitive) B cells. This protein (p56) associates with sIgM as a homodimer, is constitutively phosphorylated on tyrosine, and is coimmunoprecipitated with IgM but not IgD. The observed inability to iodinate p56 suggests it is an intracellular component of the receptor complex. Based upon its migration in one- and two-dimensional gel electrophoresis we show, however, that p56 is distinct from the blk, lyn, or fyn src family kinases that have been shown to be associated with sIgM in mature B cells. The developmentally regulated participation of p56 in the B cell antigen receptor complex suggests a role in the differential signaling mediated via sIgM on immature and mature B cells.
Yellen-Shaw
A J
AJ
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104.
Monroe
J G
JG
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D007072:Immunoglobulin D / Q000378:metabolism; D007075:Immunoglobulin M / Q000378:metabolism*; D051379:Mice; D008970:Molecular Weight; D011233:Precipitin Tests; D011505:Protein-Tyrosine Kinases / Q000032:analysis; D011817:Rabbits; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D011961:Receptors, Fc / Q000032:analysis*
D007072:Immunoglobulin D; D007075:Immunoglobulin M; D011947:Receptors, Antigen, B-Cell; D011961:Receptors, Fc; C035311:immunoglobulin M receptor; D011505:Protein-Tyrosine Kinases