CD38 ligation induces tyrosine phosphorylation of Bruton tyrosine kinase and enhanced expression of interleukin 5-receptor alpha chain: synergistic effects with interleukin 5.
Mouse CD38 has been implicated in the regulation of both B-cell proliferation and protection of B cells from irradiation-induced apoptosis. CD38 ligation on B cells by CS/2, an anti-mouse CD38 monoclonal antibody, induced proliferation, IgM secretion, and tyrosine phosphorylation of Bruton tyrosine kinase in B cells from wild-type mice. B cells from X chromosome-linked immunodeficient mice did not respond at all to anti-CD38 antibody, although CD38 expression on these B cells was comparable to that on wild-type B cells. We infer from these results that Bruton tyrosine kinase activation is involved in B-cell triggering after cross-linkage of CD38. Analysis of the synergistic effects of various cytokines with CD38 ligation on B-cell activation revealed that interleukin 5 (IL-5) showed the most potent effect on B-cell proliferation, Blimp1 gene expression, and IgM production. These synergistic effects were not seen with B cells from X chromosome-linked immunodeficient mice. Flow cytometry analysis revealed that CD38 ligation increased surface expression of the IL-5-receptor alpha chain on B cells. These data indicate that CD38 ligation increases IL-5 receptor alpha expression and synergizes with IL-5 to enhance Blimp1 expression and IgM synthesis.
Department of Immunology, University of Tokyo, Japan.
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Y
Kikuchi
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Yasue
K
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Miyake
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M
Kimoto
K
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Takatsu
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D000077329:Agammaglobulinaemia Tyrosine Kinase; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation / Q000187:drug effects; D003432:Cross-Linking Reagents; D004357:Drug Synergism; D004789:Enzyme Activation; D008040:Genetic Linkage; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D007107:Immune System / Q000002:abnormalities; D007075:Immunoglobulin M / Q000378:metabolism; D015848:Interleukin-5 / Q000494:pharmacology*; D007378:Interleukins / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000235:genetics; D008562:Membrane Glycoproteins; D051379:Mice; D008810:Mice, Inbred C57BL; D009699:N-Glycosyl Hydrolases / Q000276:immunology*; D010766:Phosphorylation; D000074462:Positive Regulatory Domain I-Binding Factor 1; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D018123:Receptors, Interleukin / Q000378:metabolism*; D053649:Receptors, Interleukin-5; D012097:Repressor Proteins; D015398:Signal Transduction; D013154:Spleen / Q000166:cytology / Q000276:immunology; D014157:Transcription Factors / Q000235:genetics; D014960:X Chromosome
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; D003432:Cross-Linking Reagents; D007075:Immunoglobulin M; D015848:Interleukin-5; D007378:Interleukins; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; C513258:Prdm1 protein, mouse; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D053649:Receptors, Interleukin-5; D012097:Repressor Proteins; D014157:Transcription Factors; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D000074462:Positive Regulatory Domain I-Binding Factor 1; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625951:Btk protein, mouse; D009699:N-Glycosyl Hydrolases; D036541:ADP-ribosyl Cyclase; C498155:Cd38 protein, mouse; D051997:ADP-ribosyl Cyclase 1