Intravenous Ig Regulates Anti-Desmoglein 3 IgG Production in B220^– Antibody-Producing Cells in Mice with Pemphigus Vulgaris

Intravenous Ig (IVIG) is a treatment option for intractable cases of pemphigus vulgaris (PV), an autoimmune blistering disease caused by autoantibodies against desmoglein 3 (DSG3). To investigate the efficacy of IVIG on autoantibody secretion, we produced PV model mice by adoptive transfer of immunized Dsg3^−/− splenocytes to Rag2^−/− mice. We found that circulating anti-DSG3 IgG ELISA titer decreased in PV model mice after 5 days of treatment with IVIG compared with PBS-treated mice, whereas the F(ab’)₂ fragment did not suppress the anti-DSG3 IgG titer. enzyme-linked immunospot assay revealed that IVIG treatment reduced the frequency of anti-DSG3 antibody–secreting cells in the spleen but not in lymph nodes and bone marrow. Moreover, this reduction was observed only in the splenic B220⁻ fraction but not in the B220⁺ fraction. Furthermore, IVIG decreased the serum levels of anti-DSG3 IgG, even after a significant reduction of its titer, owing to antibody-mediated CD20⁺ B cell depletion. In addition, IVIG suppressed anti-DSG3 IgG production in B220⁻CD138⁺ plasma cells derived from PV model mice ex vivo. These results indicate that IVIG reduced autoantibody production in B220⁻ cells containing plasma cells in PV model mice, and this function may indicate one of the mechanisms of action of IVIG on PV.