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CD40L is crucial for the development of autoimmunity induced by TLR7 overexpression
Author(s) -
Pisitkun Prapaporn,
Deane Jonathan A.,
Bolland Silvia
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.668.22
Subject(s) - germinal center , tlr7 , autoimmunity , cd40 , immunology , b cell , biology , phenotype , antibody , immune system , toll like receptor , in vitro , gene , genetics , innate immune system , cytotoxic t cell
Antibodies against nuclear antigens secreted by autoreactive B cells are a hallmark of systemic autoimmunity. Failure to eliminate autoreactive B cells in the germinal center reaction has been reported in lupus disease. We have shown that control of TLR7 expression is essential to restrict B cell autoimmunity and DC expansion. However, the underlying mechanisms of TLR7‐induced autoimmunity still need to be scrutinized. We found increased spontaneous germinal center formation in Tg.TLR7 mice. B cells from these mice showed enhanced H2‐Ab1, stat1, T‐bet, AID expression and increased IgG1 and IgG2b immunoglobulin transcript. To test whether these B cell phenotypes required T cell help, we bred Tg.TLR7 with CD40L deficient mice. In the absence of CD40L, Tg.TLR7 mice did not develop spontaneous germinal center or any autoimmune phenotypes. Reconstitution experiments with an equal mix of Tg.TLR7.CD40L−/− and WT bone marrow showed that CD40L provided in trans can induced the disease. All of these results suggest that autoreactive B cell and autoimmune phenotype of Tg.TLR7 mice is CD40L‐dependent. Future experiments will determine whether T cells are needed to provide help through CD40L in this system.