Regulation of B-cell immune responses: predominant role of interleukin-4 in triggering cell proliferation and Ig production in competent B cells.

We established a system for induction of competence in B cells following brief (45 min) exposure to either the combination of phorbol 12,13-dibutyrate (PDB) and ionomycin (I) (PDB/I) or PDB/anti-IgM. B cells, rendered competent in this fashion, were able to respond to PDB in the second or progression phase of culture but did not proliferate on their own. In addition, competent B cells were IL-2- or IL-4-responsive, due to up-regulation of their respective receptors following competence induction. IL-4 was found to have the most effective role in the progression phase to promote DNA synthesis and was able to enhance both IL-2 and IL-4 receptor expression. Whereas provision of IL-4 could induce IgM, IgG, and IgA in the absence of T cells, it did not result in IgE production. IgE production was only achieved in the presence of activated T cells (competent) together with competent B cells. These results indicate that IL-4 has a major role in B-cell immune responses following initial activation and trigger the cells, in the absence of T cells or other factors, to proliferate and differentiate into Ig-secreting cells. For IgE production in competent B cells, however, IL-4 alone could not overcome the requirement for activated T cells.