BAFF induces CXCR5 expression during B cell differentiation in bone marrow.

B cell activating factor (BAFF) plays an important role in antibody production through differentiation and maturation of B cells mainly in secondary lymphoid organs. On the other hand, the role of BAFF in the bone marrow, the primary lymphoid organ of B cell development, has not been well elucidated. Here, effects of BAFF in bone marrow B cell development were examined by using BAFF-deficient mice. When mRNA expression levels of B cell differentiation markers including , , , and were compared between bone marrow of wild-type and BAFF-KO mice, a lower level of expression was found in the KO mice. Additionally, protein expression of CXCR5 on IgM cells in the bone marrow was decreased by BAFF deficiency. In vitro studies also confirmed the effect of BAFF on CXCR5 by IgM cells; culturing bone marrow cells from BAFF-KO mice with BAFF in vitro increased the proportion of CXCR5 cells in IgM cells compared with non-treated bone marrow cells. In addition, BAFF synergized with TNF-α and IL-6 to increase the expression of CXCR5 on IgM cells. The BAFF-mediated up-regulation of CXCR5 expression was reproduced by using CD19 cells purified from BAFF-KO bone marrow cells, suggesting that BAFF directly affects B-lineage cells in bone marrow to promote CXCR5 expression. Together, this study suggests that BAFF has an important role in B cell differentiation in bone marrow by directly inducing CXCR5 expression which affect their migration to secondary lymphoid organs.