Differential regulation of mouse B cell development by transforming growth factor beta1.

Denise A Kaminski,Peter D Burrows,John J Letterio

doi:10.1080/1044667031000088057

Denise A Kaminski, Peter D Burrows + Show 1 more

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https://doi.org/10.1080/1044667031000088057

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Abstract

Transforming growth factor β (TGFβ) 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 TGFβ1-/- mice. To evaluate TGFβ responsiveness during normal B lineage development, cells were cultured in interleukin 7 (IL7)±TGFβ. Picomolar doses of TGFβ1 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 TGFβ1. 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 TGFβ1 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.

Highlights

Transforming growth factor b (TGFb) is distinguished among cytokines in its involvement in multiple biological processes, eliciting unique responses according to context (Massague et al, 1992; Rifkin et al, 1993; McCartneyFrancis and Wahl, 1994; Bottinger et al, 1997)
The 1.5 weekold TGFb12/2 mice were comparable to the TGFb1þ/þ littermate (LM) controls at the early, sIgM2 and later, sIgMþ stages
The cell surface marker system described by Hardy et al (1991) was used to further define the B lineage developmental stages affected by the TGFb1 deficiency, and the results were calculated both as a percentage of total bone marrow (BM) (Fig. 2A,B) and as absolute cell numbers (Fig. 2C)

Summary

Introduction

Transforming growth factor b (TGFb) is distinguished among cytokines in its involvement in multiple biological processes, eliciting unique responses according to context (Massague et al, 1992; Rifkin et al, 1993; McCartneyFrancis and Wahl, 1994; Bottinger et al, 1997). Its overlapping functions include regulation of embryogenesis (Dickson et al, 1995; Kaartinen et al, 1995; Bonyadi et al, 1997; Sanford et al, 1997), cell cycle and viability (Ravitz and Wenner, 1997; Hocevar and Howe, 1998) and cellular adhesion (Roberts et al, 1992; Wahl, 1994; Kim and Yamada, 1997; Letterio and Roberts, 1998) The interplay of these TGFb-regulated processes controls the development and function of the immune system (Yaswen et al, 1996; Letterio and Roberts, 1998; Larsson et al, 2001)

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