differential regulation of mouse b cell development by transforming growth factor β1鼠标微分调节b细胞转化生长因子β1发展.pdfVIP

Developmental Immunology, 2002 Vol. 9 (2), pp. 85–95 Differential Regulation of Mouse B Cell Development by Transforming Growth Factor b1 DENISE A. KAMINSKIa,*, JOHN J. LETTERIOb and PETER D. BURROWSa,† aDepartment of Microbiology, 378 Wallace Tumor Institute, The University of Alabama at Birmingham, Birmingham, AL 35294, USA; bLaboratory of Cell Regulation and Carcinogenesis, The National Cancer Institute, 41 Library Drive, Bethesda, MD 20892, USA (Revised 4 January 2003) Transforming growth factor b (TGFb) can inhibit the in vitro proliferation, survival and differentiation of B cell progenitors, mature B lymphocytes and plasma cells. Here we demonstrate unexpected, age- dependent reductions in the bone marrow (BM) B cell progenitors and immature B cells in TGFb12/ 2 mice. To evaluate TGFb responsiveness during normal B lineage development, cells were cultured in interleukin 7 ðIL7Þ ^TGFb: Picomolar doses of TGFb1 reduced pro-B cell recoveries at every timepoint. By contrast, the pre-B cells were initially reduced in number, but subsequently increased compared to IL7 alone, resulting in a 4-fold increase in the growth rate for the pre-B cell population. Analysis of purified BM sub-populations indicated that pro-B cells and the earliest BP12 pre-B cells were sensitive to the inhibitory effects of TGFb1. However, the large BP1þ pre-B cells, although initially reduced, were increased in number at days 5 and 7 of culture. These results indicate that TGFb1 is important for normal B cell development in vivo, and that B cell progenitors are differentially affecte