Mechanism of inhibition of lipopolysaccharide-stimulated mouse B-cell responses by transforming growth factor-beta 1

Abstract

Transforming growth factor-beta 1 (TGF beta 1) is a pleiotropic cytokine which inhibits growth of many cell types and positively or negatively regulates the production of Ig isotypes. By using mouse resting B cells stimulated by lipopolysaccharide (LPS), we investigated whether the effect of TGF beta 1 on Ig production is related to its effect on cell growth. We show that low doses of TGF beta 1 stimulate IgG3 and IgG2b production whereas higher doses inhibit IgM, IgG3, IgG1 and IgG2b secretion and cell proliferation. TGF beta 1 titration curves and kinetics experiments suggested that the inhibitory effect on Ig secretion and B-cell growth are closely related. We defined the phase at which TGF beta 1 exerts its anti-proliferative effect on mouse B cells. TGF beta 1 does not modify the increase in expression of class II antigens which occurs before transition from G0 to G1. However, it partially inhibits the induction of expression of low-affinity Fc gamma RII and cell enlargement which both begin during the early G1 phase, and it totally blocks induction of the expression of transferrin receptors, a marker of the late G1 phase. Thus, TGF beta 1 blocks LPS-stimulated mouse B cells in the early G1 phase, and this results in inhibition of Ig production.