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Tonic B cell activation by Radioprotective105/MD-1 promotes disease progression in MRL/lpr mice

Kobayashi, Toshihiko
Takahashi, Koichiro
Nagai, Yoshinori
Shibata, Takuma
Akira, Shizuo
Gotoh, Yoshiyuki
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Published in International immunology. 2008, vol. 20, no. 7, p. 881-91
Abstract Toll-like receptors (TLRs) have a crucial role in sensing microbial products and triggering immune responses. Recent reports have indicated that TLR7 and TLR9 have an important role in activating autoreactive B cells. In addition to TLR7 and TLR9, mouse B cells express TLR2, TLR4 and structurally related Radioprotective105 (RP105). We have previously shown that RP105 works in concert with TLR2/4 in antibody response to TLR2/4 ligands. We here report that B cells are constitutively activated by TLR2/4 and RP105. Such B cell activation was revealed by the gamma3 germ line transcript and serum IgG3 production, both of which were impaired by the lack of RP105 or TLR2/4. Serum IgG3 was not altered in germ-free or antibiotics-treated mice, suggesting that the microbial flora hardly contributes to the continuous activation of B cells. The lack of RP105-dependent B cell activation ameliorated disease progression in lupus-prone MRL/lpr mice. RP105(-/-) MRL/lpr mice showed less lymphoadenopathy/splenomegaly and longer survival than MRL/lpr mice. Whereas glomerulonephritis and auto-antibody production were not altered, improvement in blood urea nitrogen and lower incidence of renal arteritis indicated that renal function was ameliorated in the absence of RP105. Our results suggest that RP105-dependent tonic B cell activation has a pathogenic role in MRL/lpr mice.
Keywords AnimalsAntigens, CD/immunologyAutoantibodies/blood/genetics/immunologyB-Lymphocytes/immunology/metabolismDisease ProgressionFemaleGlomerulonephritis/blood/immunology/physiopathologyImmunoglobulin G/blood/immunologyLupus Erythematosus, Systemic/blood/immunology/physiopathologyLymphocyte Activation/immunologyMiceMice, Inbred C57BLMice, Inbred MRL lprMice, KnockoutSignal Transduction/immunologySpecific Pathogen-Free Organisms/immunologyToll-Like Receptors/immunology
PMID: 18492657
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Research group Lupus érythémateux systémique, de l'anémie hémolytique et de la glomérulonéphrite (168)
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KOBAYASHI, Toshihiko et al. Tonic B cell activation by Radioprotective105/MD-1 promotes disease progression in MRL/lpr mice. In: International immunology, 2008, vol. 20, n° 7, p. 881-91. doi: 10.1093/intimm/dxn049 https://archive-ouverte.unige.ch/unige:2104

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Deposited on : 2009-06-19

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