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55 Response gene to complement-32 promotes plasma cell differentiation and enhances lupus-like chronic graft versus host disease
  1. H Rus1,
  2. A Tatomir1,
  3. V Nguyen2,
  4. C Cudrici3,
  5. T Badea4 and
  6. V Rus2
  1. 1University of Maryland School of Medicine, Neurology, Baltimore, USA
  2. 2University of Maryland School of Medicine, Medicine, Baltimore, USA
  3. 3National Institute of Health, NIAMS, Bethesda, USA
  4. 4National Institute of Health, NEI, Bethesda, USA


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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