Regulation of the B cell immune response: induction of competence and progression in a surface IgM-bearing subset.

We have targeted the specific surface IgM-bearing subset of human B lymphocytes within a mixed population and investigated cell cycle activation in these cells stimulated with phorbol ester and antibody directed against surface immunoglobulin. Stimulation with phorbol 12,13-dibutyrate (PDB) in combination with anti-IgM led to induction of the state of competence followed by progression to proliferation of the surface IgM-bearing cells. In contrast, sequential stimulation with PDB and anti-IgM in either order did not induce either competence or progression. Brief exposure to both stimuli for 30 min did not induce significant proliferation, but did induce the state of competence such that the cells progressed to DNA synthesis after incubation with PDB alone. Furthermore, a competence-related gene, c-fos, was induced in cells that did not become fully competent. Thus, induction of competence to proliferate required simultaneous delivery of two signals whereas actual progression to proliferation by competent cells was accomplished with only one signal.