INFLUENCE OF TRANSFORMING GROWTH-FACTOR-BETA (TGF-BETA) ON THE IMMUNOGLOBULIN PRODUCTION BY EBV-INFECTED B-CELL CULTURES

TGF-beta inhibits the proliferation of human B lymphocytes stimulated by a variety of activators, including EBV. However, EBV-immortalised cells are refractory to TGF-beta. The influence of TGF-beta on B cell maturation varies, apparently depending on the origin of the B lymphocytes and their maturation/activation state, the strength of the stimulus and the presence of cofactors. We investigated the effect of TGF-beta on immunoglobulin production by 5-day-old EBV-infected B cells. TGF-beta added at the initiation of the cultures inhibited IgM, IgG and IgA secretion by decreasing the numbers of secretory cells. The inhibition of IgM secretion was strongest. At the cytoplasmic level, TGF-beta reduced the expression of IgM heavy, lambda and kappa light chains but not IgG and IgA heavy chains. However, the IgM production by an established EBV-transformed B cell line was not affected by TGF-beta. Thus, TGF-beta inhibited EBV-induced maturation of the B cells until they acquired a transformed state. We discuss the relevance of these findings for the potential role of TGF-beta on EBV infection.