Stimulation of B-cell proliferation by membrane-associated molecules from activated T cells.

Activation of B cells to proliferation and antibody secretion is dependent on soluble lymphokines secreted by activated T cells. Activation of T cells results from physical contact between B cells and T cells through binding of the T-cell antigen receptor to a complex of antigen and class II major histocompatibility complex (MHC) molecules. To determine whether this interaction also contributes to B-cell activation by mechanisms other than those mediated by soluble T cell-derived lymphokines, I examined the ability of isolated T-cell plasma membranes to stimulate proliferation in cultures of unfractionated B cells. Membranes prepared from a cloned antigen-specific helper T-cell line induced substantial proliferation provided that the T cells had been mitogen-activated before isolation of membranes. Membranes from splenic Con A-treated blasts also stimulated B-cell proliferation, suggesting that this activity may be a common property of some subsets of activated T cells. Induction of B-cell proliferation was not found to be antigen-dependent or MHC-restricted, indicating no significant contribution by the T-cell receptor for antigen. The presence of interleukins 4 and 5 in membrane fractions was indicated by proliferation of lymphokine-sensitive cell lines, although culture supernatants from mitogen-activated T cells proved to be far more potent sources of these activities. The combined effect of membranes and lymphokine-containing culture supernatants in B-cell cultures was greater than their added effects in separate cultures. This observation suggests that lymphokines or molecules with mitogenic activity for B cells other than those found in abundance in culture supernatants may be present on activated T-cell membranes.