Inhibition of IgG1 and IgE production by stimulation of the B cell CTLA-4 receptor.
Although a large amount of information is available on the activity of CTLA-4 in T cells, the role of this receptor in B cells has not been previously characterized. Our results show that CD40 or LPS stimulation in the presence of IL-4 induces CTLA-4 expression in purified B cells; the maximum level is reached in both membrane and intracellular compartments after 48-72 h. Engagement of the B cell CTLA-4 by immobilized mAb inhibits IgG1 and IgE production and reduces the frequency of IgG1- and IgE-expressing B cells. Cepsilon and Cgamma(1) germline mRNA expression as well as NF-kappaB and STAT6 activation, events required for isotype switching, are also inhibited by CTLA-4 engagement. Together these findings show the critical role of CTLA-4 in the control of IL-4-driven isotype switching and suggest new approaches for modulating immediate-type hypersensitivity responses.
Pioli
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C
Section of Toxicology and Biomedicine, Ente per le Nuove Tecnologie, l'Energia et l'Ambiente C.R. Casaccia., Rome, Italy. pioli@casaccia.enea.it
Gatta
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L
Ubaldi
V
V
Doria
G
G
D000069594:Abatacept; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism* / Q000502:physiology; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D019013:CD40 Antigens / Q000276:immunology; D060908:CTLA-4 Antigen; D002478:Cells, Cultured; D015536:Down-Regulation / Q000276:immunology; D018796:Immunoconjugates; D007127:Immunoglobulin Constant Regions / Q000096:biosynthesis / Q000235:genetics; D007073:Immunoglobulin E / Q000096:biosynthesis*; D007074:Immunoglobulin G / Q000096:biosynthesis*; D007075:Immunoglobulin M / Q000096:biosynthesis; D007139:Immunoglobulin epsilon-Chains / Q000096:biosynthesis / Q000235:genetics; D015847:Interleukin-4 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D018655:Lymphocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D017455:Receptors, IgE / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D050800:STAT6 Transcription Factor; D015398:Signal Transduction / Q000276:immunology; D015534:Trans-Activators / Q000037:antagonists & inhibitors / Q000378:metabolism
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; D019013:CD40 Antigens; D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; D018796:Immunoconjugates; D007127:Immunoglobulin Constant Regions; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007139:Immunoglobulin epsilon-Chains; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012333:RNA, Messenger; D017455:Receptors, IgE; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D015534:Trans-Activators; D015847:Interleukin-4; D007073:Immunoglobulin E; D000069594:Abatacept