Differential regulation of mouse B cell development by transforming growth factor beta1.
Transforming growth factor beta (TGFbeta) 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 TGFbeta1-/- mice. To evaluate TGFbeta responsiveness during normal B lineage development, cells were cultured in interleukin 7 (IL7) +/- TGFbeta. Picomolar doses of TGFbeta1 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 BP1- pre-B cells were sensitive to the inhibitory effects of TGFbeta1. However, the large BP1+ pre-B cells, although initially reduced, were increased in number at days 5 and 7 of culture. These results indicate that TGFbeta1 is important for normal B cell development in vivo, and that B cell progenitors are differentially affected by the cytokine according to their stage of differentiation.
Department of Microbiology, 378 Wallace Tumor Institute, The University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Denise A
DA
Kaminski
John J
JJ
Letterio
Peter D
PD
Burrows
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000276:immunology*; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D005260:Female; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016212:Transforming Growth Factor beta / Q000172:deficiency / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D053773:Transforming Growth Factor beta1
C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1