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.
Kaminski
Denise A
DA
Department of Microbiology, 378 Wallace Tumor Institute, The University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Letterio
John J
JJ
Burrows
Peter D
PD
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