B cells regulate thymic CD8⁺T cell differentiation in lupus-prone mice

Previous studies have shown that under normal physiological conditions thymic B cells play a critical function in T cell negative selection. We tested the effect of thymic B cells on thymic T-cell differentiation in autoimmune diseases including systemic lupus erythematosus (SLE). We found that thymic B cells and CD8^- CD4⁺ and CD4^-CD8⁺T cells increased, whereas CD4⁺CD8⁺T cells decreased in lupus-prone mice. Once B cells were reduced, the change was reversed. Furthermore, we found that B cells blocked thymic immature single positive (ISP) CD4^-CD8⁺CD3^lo/-RORγt^- T cells progression into CD4⁺CD8⁺T cells. Interestingly, we found a novel population of thymic immature T cells (CD4^-CD8⁺CD3^loRORγt⁺) that were induced into mature CD4^-CD8⁺CD3⁺RORγt⁺T cells by B cells in lupus-prone mice. Importantly, we found that IgG, produced by thymic B cells, played a critical role in the differentiation of thymic CD8⁺ISP and mature RORγt⁺CD8⁺ T cells in lupus-prone mice. In conclusion, B cells blocked the differentiation from thymic CD8⁺ISP and induced the differentiation of a novel immature CD4^-CD8⁺CD3^loRORγt⁺T cells into mature RORγt⁺CD8⁺ T cells by secreting IgG antibody in lupus-prone mice.