Beta transforming growth factors are potential regulators of B lymphopoiesis.

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Abstract
Members of the transforming growth factor .beta. (TGF-.beta.) family of polypeptides were found to be potent in vitro inhibitors of K light chain expression on normal bone marrow-derived and transformed cloned pre-B cells, and of the maturation of these cells to mitogen responsiveness. The inhibition by TGF-.beta. was selective in that Ia expression was not blocked. Together with the observations that LPS, IL-1, NZB serum factors, IL-4, and IFN-.gamma. preferentially induced either K or Ia, or both, on a pre-B cell line, these results further suggest that acquistion of Ig and class II molecules is independently controlled by different antagonists as well as agonists. In addition, K chain induction by IFN-.gamma. does not appear to be as sensitive to TGF-.beta. downregulation as that stimulated by other factors tested, and this raises the possibility that activation of the same gene may result from different transmembrane signaling pathways. In contrast to the inhibitory effects of TGF-.beta. on K acquisition by pre-B cells and on K increase after exposure of mature B cells to LPS, as measured by K RNA levels and/or surface fluorescence, no inhibition was observed on unstimulated spleen B cells or on two cloned B cell lines that constitutively produce K. Thus, TGF-.beta. may function during specific stages of B cell differentiation by inhibiting initiation of, or increased transcription of Ig genes, and therefore, may be an important negative regulator of B lymphopoiesis. It is the first natural substance found to have this effect.