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)/-ROR gamma t-T cells progression into CD4(+)CD8(+) T cells. Interestingly, we found a novel population of thymic immature T cells (CD4(-)CD8(+)CD3(lo)ROR gamma t(+)) that were induced into mature CD4(-)CD8(+) CD3(+)ROR gamma t(+)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 ROR gamma t(+) 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(lo)ROR gamma t(+) T cells into mature ROR gamma t(+) CD8(+) T cells by secreting IgG antibody in lupus-prone mice.