Activation events in hapten-specific B cells from tolerant mice.
We have studied hapten-binding cells from the spleens of normal and tolerant adult mice in terms of their ability to enlarge, proliferate, and differentiate into antibody-secreting cells. Tolerant B cells showed clear defects in intermediate activation events in addition to a deficit in antibody-secreting cells. In these studies, isolated B cells were stimulated by T cell independent Ag with lymphokines, or with mitogens, in the absence of filler cells. The number of antibody-secreting cells generated from the tolerant population was consistently reduced by 70 to 80% of the control response to the specific Ag, fluoresceinated Brucella abortus (FL-BrA) +/- lymphokines. We found that similar numbers of normal and tolerant cells enlarged (entered cell cycle) when stimulated by FL-BrA, LPS, IL-4, or alpha-Ig coupled to dextran (alpha-Ig-dex). Ia induction stimulated by IL-4, LPS, FL-BrA, or alpha-Ig-dex was the same in normal and tolerant cells. However, DNA synthesis stimulated by FL-BrA, FL-BrA + IL-5, or suboptimal concentrations of LPS was reduced by 70% in the tolerant cell population. Proliferation in response to 50 micrograms/ml LPS or to low doses of alpha-Ig-dex was similar in normal and tolerant B cells. These data suggest that the primary defect in adult B cell tolerance is the ability to proliferate in response to Ag.
Chace
J H
JH
Department of Microbiology and Immunology, University of Rochester Medical Center, NY 14642.
Scott
D W
DW
D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D000942:Antigens, Bacterial / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D001666:Binding Sites, Antibody; D002003:Brucella abortus / Q000276:immunology; D000939:Epitopes / Q000276:immunology*; D005434:Flow Cytometry; D005452:Fluoresceins; D006241:Haptens / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D007108:Immune Tolerance; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D000939:Epitopes; D005452:Fluoresceins; D006241:Haptens; D000949:Histocompatibility Antigens Class II