Background and aims Response Gene to Complement (RGC) −32 plays an important role in cell cycle activation. Our prior studies showed that RGC-32 promotes Th17 differentiation of CD4 T cells. We used wild-type (WT) and RGC-32 knockout (KO) mice to determine whether lack of RGC-32 impairs B cell differentiation and activation and alters autoimmune parameters in the chronic graft versus host disease (cGVHD) model of lupus.
Methods TLR-dependent and T dependent B cell differentiation to plasma cells (PC) was induced with LPS and with CD40mAb plus IL-4. cGVHD was induced with 100×106 Bm12 splenocytes injected into WT or RGC-32 KO recipients.
Results RGC-32 KO B cells failed to differentiate normally to PC as demonstrated by a 2-fold reduction in PC numbers generated after stimulation and impaired upregulation of Prdm1 and IRF4 mRNA. RGC-32 transcripts were upregulated in spleen cells from cGVHD mice and protein expression was detected in B cells and germinal centre (GC) cells. RGC-32 KO hosts displayed an attenuated autoimmune phenotype as demonstrated by decreased production of anti-dsDNA autoantibodies and proliferation of germinal centre B cells. In addition a decreased number of IgG anti-dsDNA secreting PC and IRF4 and Prdm1 mRNA expression were found
Conclusions These results suggest that expression of RGC-32 in B cells is critical for optimal GC proliferation, PC differentiation and autoantibody production in a murine model of lupus. These data support the idea that RGC-32 blockade has the potential to attenuate autoimmune parameters of cGVHD and possibly reverse abnormalities in the T and B cell that contribute to lupus pathogenesis.
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