POLYCLONAL ACTIVATION OF IMMATURE B-CELLS BY PREACTIVATED T-CELLS - THE ROLE OF IL-4 AND CD40-LIGAND

It is well-established that preactivated CD4+ T cells can activate mat ure B cells in a polyclonal, MHC-unrestricted fashion. We have used th is system to investigate the effects of T cell-derived signals on imma ture B cells purified from the spleens of neonatal mice, since these c ells are unresponsive to many polyclonal activators and are exquisitel y sensitive to tolerization. We show that immature B cells can be indu ced to proliferate by anti-CD3 activated, fixed T(h)1 and T(h)2 cells, although the latter induce a greater response than the former. Antibo dies to IL-4 partially blocked stimulation by T(h)2 cells, whereas ant ibodies to IL-2 and IL-5 had no effect on responses to T(h)1 cells. Th is suggested that molecules in addition to IL-4 contribute to the capa city of T cells to induce B cell activation, one likely candidate bein g the ligand for CD40. We therefore generated mouse erythroleukemia (M EL) transfectants which express CD40 ligand (CD40L). These transfectan ts also induced proliferation of immature B cells, which is enhanced b y IL-4. Unlike the situation with mature B cells, both anti-mu and ant i-delta antibodies inhibited the activation of immature B cells by CD4 0L-MEL cells. However, this inhibition was reversed by IL-4, which syn ergized with signals delivered through CD40 to render immature B cells refractory to negative signals delivered through slg. Taken together these data suggest that immature B cells can be activated by T cell-de rived contact signals and that CD40L - CD40 interactions, in the prese nce of IL-4, are capable of abrogating the negative signals generated via slgM and slgD receptors expressed by these cells.