Relative contributions of b cells and dendritic cells from lupus-Prone mice to CD4 ⁺ t cell polarization

Mouse models of lupus have shown that multiple immune cell types contribute to autoimmune disease. This study sought to investigate the involvement of B cells and dendritic cells in supporting the expansion of inflammatory and regulatory CD4 ⁺ T cells that are critical for lupus pathogenesis. We used lupus-prone B6.NZM2410.Sle1.Sle2.Sle3 (TC) and congenic C57BL/6J (B6) control mice to investigate how the genetic predisposition of these two cell types controls the activity of normal B6 T cells. Using an allogeneic in vitro assay, we showed that TC B1-a and conventional B cells expanded Th17 cells significantly more than their B6 counterparts. This expansion was dependent on CD86 and IL-6 expression and mapped to the Sle1 lupus-susceptibility locus. In vivo, TC B cells promoted greater differentiation of CD4 ⁺ T cells into Th1 and follicular helper T cells than did B6 B cells, but they limited the expansion of Foxp3 regulatory CD4 ⁺ T cells to a greater extent than did B6 B cells. Finally, when normal B6 CD4 ⁺ T cells were introduced into Rag1 ² / ² mice, TC myeloid/stromal cells caused their heightened activation, decreased Foxp3 regulatory CD4 ⁺ T cell differentiation, and increased renal infiltration of Th1 and Th17 cells in comparison with B6 myeloid/ stromal cells. The results show that B cells from lupus mice amplify inflammatory CD4 ⁺ T cells in a nonredundant manner with myeloid/stromal cells. The Journal of Immunology, 2018, 200: 3087–3099.