Negative signaling via FcgammaRIIB1 in B cells blocks phospholipase Cgamma2 tyrosine phosphorylation but not Syk or Lyn activation.
Crosslinking of the B cell antigen receptor surface immunoglobulin induces tyrosine phosphorylation and activation of the Src family and Syk tyrosine protein kinases, tyrosine phosphorylation of phospholipase Cgamma2 (PLCgamma2) and increases in intracellular second messengers inositol phosphates and Ca2+. These activation events, in conjunction with other pathways, culminate in the induction of B cell proliferation and differentiation. In contrast, co-crosslinking surface Ig with the B cell IgG Fc receptor prevents many of these activation events, including B cell proliferation and differentiation. The precise nature of the negative signal(s) derived from Fc receptors that prevent B cell activation is not known. Here, early activation events were examined in B cells stimulated via the antigen receptor alone or under co-crosslinking conditions. The data indicated a selective block in the tyrosine phosphorylation and activation of PLCgamma2 but not in activation of the upstream kinases, Syk and Lyn, under co-crosslinking conditions. We conclude that the negative signal acts directly on PLCgamma2 and is consistent with recent studies describing an activation-induced association of a phosphotyrosine phosphatase with tyrosine-phosphorylated B cell Fc receptor.
Sarkar
S
S
Ohio State University, Department of Microbiology, Columbus, Ohio 43210, USA.
Schlottmann
K
K
Cooney
D
D
Coggeshall
K M
KM
D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology*; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins; D007527:Isoenzymes / Q000378:metabolism*; D051379:Mice; D051966:Phospholipase C gamma; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011940:Receptor Aggregation; D011947:Receptors, Antigen, B-Cell / Q000502:physiology*; D017452:Receptors, IgG / Q000502:physiology*; D015398:Signal Transduction; D000072377:Syk Kinase; D010738:Type C Phospholipases / Q000378:metabolism*; D019061:src-Family Kinases / Q000378:metabolism*
D004792:Enzyme Precursors; D047908:Intracellular Signaling Peptides and Proteins; D007527:Isoenzymes; D011947:Receptors, Antigen, B-Cell; D017452:Receptors, IgG; D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; C000606897:Syk protein, mouse; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases; D010738:Type C Phospholipases; D051966:Phospholipase C gamma