Anti-immunoglobulin stimulation of B lymphocytes activates src-related protein-tyrosine kinases.
Stimulation of resting B lymphocytes with antibodies to surface immunoglobulin (sIgD or sIgM) induces protein tyrosine phosphorylation, implicating one or more B-cell protein-tyrosine kinases (PTKs) in sIg signal transduction. We have evaluated whether members of the src family of PTKs are involved in this process. Our results show that addition of antibodies to IgD or to IgM can stimulate the PTK activity of the blk, fyn, and lyn gene products. Additionally, all three PTKs were found to coimmunoprecipitate with sIg in digitonin lysates from resting B cells. In all stimulatory conditions, whether initiated through sIgD or sIgM, the blk gene product p56blk displayed the strongest activation index. The kinetics of activation of these kinases, particularly that of p56blk, paralleled the early appearance of newly tyrosine-phosphorylated B-cell proteins, suggesting that this group of kinases may account for some portion of the tyrosine kinase activity in sIg-activated B cells. These observations demonstrate a functional and possible physical association between the members of the src family of PTKs and the B-cell antigen receptors.
Burkhardt
A L
AL
Laboratory of Tumor Virus Biology, National Cancer Institute, Bethesda, MD 20892.
Brunswick
M
M
Bolen
J B
JB
Mond
J J
JJ
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology*; D001402:B-Lymphocytes / Q000201:enzymology / Q000276:immunology*; D004789:Enzyme Activation; D005260:Female; D016391:Genes, src; D007072:Immunoglobulin D / Q000276:immunology*; D007075:Immunoglobulin M / Q000276:immunology; D007700:Kinetics; D008070:Lipopolysaccharides; D008213:Lymphocyte Activation; D051379:Mice; D008811:Mice, Inbred DBA; D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011947:Receptors, Antigen, B-Cell / Q000276:immunology; D015398:Signal Transduction; D013154:Spleen / Q000201:enzymology; D014443:Tyrosine / Q000031:analogs & derivatives / Q000032:analysis
D000888:Antibodies, Anti-Idiotypic; D007072:Immunoglobulin D; D007075:Immunoglobulin M; D008070:Lipopolysaccharides; D011947:Receptors, Antigen, B-Cell; D019000:Phosphotyrosine; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases