Bacterial lipopolysaccharide (LPS) induces proliferation of resting primary murine B lymphocytes and their differentiation into Ig-secreting cells. This is accompanied by an increase in the rate of Ig gene transcription and the accumulation of jp heavy chain secretory mRNA. Specific antiantigen receptor antibody (anti-p) induces resting B cells to proliferation but not differentiation. Upon addition of both LPS and anti-p to cultures, resting B cells again proliferate but do not differentiate. RNA transfer blots of the Ig mRNA 2 days after induction with LPS/anti-pz show a specific deficiency of the 2.4-kilobase (kb) pz secretory mRNA, whereas the levels of the 2.7-kb pz membrane and 1.2-kb K light chain mRNAs are as high as in cells treated with LPS alone. Between days 3 and 4 after treatment with both reagents, reductions of pA membrane and, to a smaller extent, K mRNA become apparent. As measured by nuclear run-on transcription experiments at day 2, the transcription rates ofIg pand the Ig Ktranscription units are equal in both induction experiments. Only at later stages do the LPS/anti-pt-treated cells transcribe Ig genes at a lower rate. Thus, the anti-p treatment, drastically reducing the p secretory mRNA production at early stages, represents a negative regulation occurring primarily at the posttranscriptional level.Activation of murine B cells proceeds in at least two steps leading to proliferation and, in a distinct event, to Ig secretion. The signals involved under physiological conditions seem to be mediated (i) via the antigen (Ag)-receptor, guaranteeing clonal selection, and (ii) via carrier with major histocompatibility complex (MHC) class II-mediated recognition of B cells by T cells. The latter provide either the transfer of a direct membrane signal and/or the proximity required for the transfer of T-cell-derived factors instrumental in B-cell growth and differentiation.Due to the lack of sufficient Ag-specific B cells, the detailed molecular events taking place during these individual steps cannot as yet be studied in Ag/T-helper-driven systems. Two alternative approaches are available: stimulation of B cells by (i) the polyclonal mitogen bacterial lipopolysaccharide (LPS), which, however, drives both proliferation and differentiation to Ig secretion and therefore does not allow the study of individual controls of these two steps, or