Activation and proliferation signals in mouse B cells. VI. Anti-Ig antibodies induce dose-dependent cell cycle progression in B cells.

Recent studies from several laboratories have shown that the concentrations of anti-immunoglobulin antibodies required to induce B lymphocytes to synthesize DNA are quite different from those needed to activate these cells, i.e. to cause resting B cells to leave G0. The present experiments examine this difference in detail. Thus, stimulation of DNA synthesis in mouse B cells requires prolonged (greater than 30 hr) exposures to high (greater than or equal to 10 micrograms/ml) concentrations of soluble F(ab')2 fragments of rabbit anti-Ig antibodies. However, as little as 50 ng/ml antibody caused B cells to enlarge, to express increased levels of Ia antigens, and to become primed to synthesize DNA more rapidly in response to restimulation with mitogenic concentrations of anti-Ig. The results of kinetic experiments suggested that the 'distance' that cells progress from G0 towards S depends not only on the time of exposure to anti-Ig, but also on its concentration. Concentrations of antibody less than 1 microgram/ml did not induce detectable RNA synthesis, and hence do not drive cells into the G1 phase of the cell cycle. Instead, under these conditions, B cells appear to enter a transitional, primed state (which has been termed GIT). This may well reflect the state into which T-dependent antigens drive resting B cells.