B cell developmental requirement for the Gαi2 gene

被引:105
作者
Dalwadi, H
Wei, B
Schrage, M
Su, TT
Rawlings, DJ
Braun, J
机构
[1] Univ Calif Los Angeles, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA
[2] Univ Calif Los Angeles, Mol Biol Inst, Los Angeles, CA 90095 USA
[3] Univ Washington, Dept Pediat, Seattle, WA 98195 USA
[4] Univ Washington, Dept Immunol, Seattle, WA 98195 USA
关键词
D O I
10.4049/jimmunol.170.4.1707
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Null mutation of the Galphai2 trimeric G protein results in a discrete and profound mucosal disorder, including inflammatory bowel disease (IBD), attenuation of IL-10 expression, and immune function polarized to Th1 activity. Genetic and adoptive transfer experiments have established a role for B cells and IL-10 in mucosal immunologic homeostasis and IBD resistance. In this study, we addressed the hypothesis that Galphai2 is required for the development of IL-10-producing B cells. Galphai2(-/-) mice were reduced in the relative abundance of marginal zone (MZ), transitional type 2 (T2), and B-1a B cells and significantly increased in follicular mature and B-1b B cells. Reconstitution of RAG2(-/-) mice with Galphai2(-/-) bone marrow induced an IBD-like colitis and a deficiency in absolute numbers of MZ, T2, and B-1 B cells. Thus, the Galphai2(-/-) genotype in colitis susceptibility and B cell development involved a cis effect within the hemopoietic compartment. In vitro, the B cell population of Galphai2(-/-) mice was functionally deficient in LPS-induced proliferation and IL-10 production, consistent with the exclusive capacity of T2 and MZ cell subpopulations for LPS responsiveness. In vivo, Galphai2(-/-) mice were selectively impaired for the IgM response to T-independent type II, consistent with the relative depletion of MZ and peritoneal B-1 subpopulations. Collectively, these results reveal a selective role for Gai2 in MZ and B-1 B cell development. Disorders of this Galphai2-dependent process in B cell development may represent a mechanism for IBD susceptibility. The Journal of Immunology, 2003.
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页码:1707 / 1715
页数:9
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