BAFF induces CXCR5 expression during B cell differentiation in bone marrow

Abstract

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 Cd19, Bcl2, Igμ, Il7r and Cxcr5 were compared between bone marrow of wild-type and BAFF-KO mice, a lower level of Cxcr5 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.