Spontaneous autoimmune polyneuropathy (SAP) in B7-2 knockout non-obese diabetic (NOD) mice is mediated by myelin P0-reactive Th1 cells. In this study, we investigated the role of B cells in SAP, focusing on CD19 as a potential therapeutic target. We found that P0-specific plasmablasts and B cells were increased in spleens of SAP mice compared to wild type NOD mice. Depletion of B cells and plasmablasts with anti-CD19 mAb led to attenuation of disease severity when administered at 5 mo of age. This was accompanied by decreased serum IgG and IgM levels, depletion of P0-specific plasmablasts and B cells, downregulation / internalization of surface CD19, and increased frequency of CD4+ regulatory T cells in spleens... More
Spontaneous autoimmune polyneuropathy (SAP) in B7-2 knockout non-obese diabetic (NOD) mice is mediated by myelin P0-reactive Th1 cells. In this study, we investigated the role of B cells in SAP, focusing on CD19 as a potential therapeutic target. We found that P0-specific plasmablasts and B cells were increased in spleens of SAP mice compared to wild type NOD mice. Depletion of B cells and plasmablasts with anti-CD19 mAb led to attenuation of disease severity when administered at 5 mo of age. This was accompanied by decreased serum IgG and IgM levels, depletion of P0-specific plasmablasts and B cells, downregulation / internalization of surface CD19, and increased frequency of CD4+ regulatory T cells in spleens. We conclude that B cells are crucial to the pathogenesis of SAP, and that CD19 is a promising B cell target for the development of disease modifying agents in autoimmune neuropathies.
