Lipopolysaccharide prevents apoptosis and induces responsiveness to antigen receptor cross‐linking in immature B cells

Unlike mature B cells, immature B cells are not activated in response to antigen receptor cross‐linking. To examine the mechanisms underlying this unresponsiveness, we have studied the effects of reagents that have been shown to alter the responses of immature B cells to antigen receptor stimulation. Bacterial lipopolysaccharide (LPS) is a polyclonal B‐cell activator, and has been shown to interfere with B‐cell tolerance induction in vivo and in vitro . Here we show that LPS can also overcome the unresponsiveness of immature B cells to stimulation with anti‐receptor (anti‐μ) antibodies. LPS synergizes with anti‐μ to induce a proliferative response that exceeds the response of immature B cells to LPS alone. Moreover, pretreatment of immature cells with LPS allows them to proliferate in response to subsequent stimulation with anti‐μ antibodies. This induction of responsiveness to anti‐μ requires exposure to LPS for at least 8 hr. Although the mechanisms of induction are not fully understood, one component of the LPS effect appears to involve enhancement of immature B‐cell survival in culture. Neonatal splenic B cells undergo spontaneous apoptosis at a much higher rate than mature B cells, but we have found that LPS causes a dramatic inhibition of apoptosis, even when it is present for only the first 8 hr of culture. The ability of LPS to promote survival of immature B cells and allow them to proliferate in response to antigen receptor stimulation provides a system for investigation of the biochemical mechanisms of unresponsiveness and tolerance susceptibility.