MECHANISM OF INHIBITION OF LIPOPOLYSACCHARIDE-STIMULATED MOUSE B-CELL RESPONSES BY TRANSFORMING GROWTH-FACTOR-BETA-1

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 IgG(3) and IgG(2b) production whereas higher doses inhibit IgM, IgG(3), IgG(1) and IgG(2b) 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 G(0) to G(1). However, it partially inhibits the induction of expression of low-affinity Fc gamma RII and cell enlargement which both begin during the early G(1) phase, and it totally blocks induction of the expression of transferrin receptors, a marker of the late G(1) phase. Thus, TGF beta 1 blocks LPS-stimulated mouse B cells in the early G(1) phase, and this results in inhibition of Ig production.