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-mu) antibodies. LPS synergizes with anti-mu 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-mu antibodies. This induction of responsiveness to anti-mu 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.
Wechsler-Reya
R J
RJ
Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia 19104, USA.
Monroe
J G
JG
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000276:immunology*; D016175:B-Lymphocyte Subsets / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D002470:Cell Survival / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D007108:Immune Tolerance; D008070:Lipopolysaccharides / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011947:Receptors, Antigen, B-Cell / Q000276:immunology*; D013997:Time Factors
D008070:Lipopolysaccharides; D011947:Receptors, Antigen, B-Cell