title: Analysis of antigen receptor signaling in B cells from mice with a retrovirus-induced acquired immunodeficiency syndrome.
abstract: MAIDS is a retrovirus-induced immunodeficiency syndrome in mice that has similarities to human AIDS. Because the functional defects in B cells from retroviral immunodeficiency syndromes have not been characterized in detail, we examined early and late parameters of B cell responses to IgM cross-linking in B cells from MAIDS and normal mice. Splenic B cells from mice with MAIDS have defective in vitro proliferative responses to LPS and anti-IgM-mediated stimuli, as well as to PMA plus calcium ionophore, indicating a generalized defect in proliferative response potential independent of specific receptor-mediated signaling. When early signaling parameters were analyzed in response to IgM cross-linking, it was found that calcium flux in B cells from MAIDS mice was significantly reduced; this reduction was not accounted for by quantitative differences in cell-surface IgM expression and therefore indicates a defect in early signal transduction through the IgM receptor. The tyrosine phosphorylation response to IgM cross-linking was also markedly deficient; tyrosine phosphorylation of Ig-alpha, Ig-beta, and an undefined protein of 80 kDa was detected in MAIDS B cells after anti-IgM stimulation, at levels substantially less than those observed in normal B cells. Multiple other tyrosine phosphorylation events observed in normal B cells, including phosphorylation of GTPase-activating protein, P13-kinase, and syk kinase, were not detected in MAIDS B cells in response to IgM cross-linking. The defect in tyrosine phosphorylation seemed to correlate with reduced surface IgM levels on a subpopulation of MAIDS B cells. B cells from mice expressing the MAIDS retrovirus-induced immunodeficiency thus reflect defects in early signaling through the Ag-specific IgM receptor as well as a generalized defect in proliferative responsiveness.
authors.affiliation: Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
authors.forename: L A
authors.initials: LA
authors.lastname: Selvey
authors.forename: H C
authors.initials: HC
authors.lastname: Morse
authors.forename: C H
authors.initials: CH
authors.lastname: June
authors.forename: R J
authors.initials: RJ
authors.lastname: Hodes
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology; D002118:Calcium / Q000502:physiology; D004792:Enzyme Precursors / Q000378:metabolism; D007072:Immunoglobulin D / Q000096:biosynthesis / Q000276:immunology; D007075:Immunoglobulin M / Q000096:biosynthesis / Q000276:immunology; D007152:Immunologic Capping; D047908:Intracellular Signaling Peptides and Proteins; D007476:Ionophores / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D016183:Murine Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000473:pathology; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000096:biosynthesis / Q000276:immunology*; D015398:Signal Transduction; D013154:Spleen / Q000473:pathology; D000072377:Syk Kinase; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D004792:Enzyme Precursors; D007072:Immunoglobulin D; D007075:Immunoglobulin M; D047908:Intracellular Signaling Peptides and Proteins; D007476:Ionophores; D008070:Lipopolysaccharides; D011947:Receptors, Antigen, B-Cell; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; C000606897:Syk protein, mouse; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium