1. Inhibition of IgG1 and IgE production by stimulation of the B cell CTLA-4 receptor.
- Author
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Pioli C, Gatta L, Ubaldi V, and Doria G
- Subjects
- Abatacept, Animals, Antibodies, Monoclonal pharmacology, Antigens, CD, Antigens, Differentiation biosynthesis, Antigens, Differentiation immunology, Antigens, Differentiation physiology, CD40 Antigens immunology, CTLA-4 Antigen, Cells, Cultured, Down-Regulation immunology, Immunoglobulin Constant Regions biosynthesis, Immunoglobulin Constant Regions genetics, Immunoglobulin M biosynthesis, Immunoglobulin epsilon-Chains biosynthesis, Immunoglobulin epsilon-Chains genetics, Interleukin-4 pharmacology, Lipopolysaccharides pharmacology, Lymphocyte Count, Mice, Mice, Inbred C57BL, NF-kappa B antagonists & inhibitors, NF-kappa B metabolism, RNA, Messenger antagonists & inhibitors, RNA, Messenger biosynthesis, Receptors, IgE antagonists & inhibitors, Receptors, IgE biosynthesis, STAT6 Transcription Factor, Signal Transduction immunology, Trans-Activators antagonists & inhibitors, Trans-Activators metabolism, Antigens, Differentiation metabolism, B-Lymphocytes immunology, B-Lymphocytes metabolism, Immunoconjugates, Immunoglobulin E biosynthesis, Immunoglobulin G biosynthesis
- Abstract
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.
- Published
- 2000
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