Differential responses to Ig and class II-mediated signals in splenic B cell subsets from normal and autoimmune mice.
B cells of mouse and human can be divided into distinct subpopulations, differing in distribution and phenotype. It is not known, however, whether B cell subsets respond similarly to signals mediated by cognate interactions with T cells, such as ligation of the B cell class II MHC molecule. Mouse splenic B cells proliferate in response to a combination of non-mitogenic anti-mu mAb, IL-4 and class II MHC-specific mAbs. In order to assess the response of B cell subpopulations to these signals, B cells were separated on the basis of CD23 expression. Previous studies have shown that CD23 expression is useful in distinguishing marginal zone from follicular B cells and peritoneal B1 from B2 B cells. B cells of both subsets responded to the combination of signals, but CD23- B cells showed a higher response. Splenic B cells were also purified from several strains of autoimmune mice, of interest because their disease features expansion of CD23- B cells and autoantibody production. While normal B cells showed no response to non-mitogenic anti-mu mAb alone, B cells from autoimmune mice showed a marked decrease in proliferation. Addition of IL-4 plus class II-specific mAbs restored increased proliferation. Again, responses were higher in CD23- than in CD23+ B cells. These findings suggest that CD23- B cells are especially responsive to signals delivered through class II and the IL-4 receptor. These signals may allow preferential rescue of CD23-B cells from antigen-mediated tolerance and result in their hyperexpansion in response to autoreactive T cells.
Bishop
G A
GA
Department of Microbiology, University of Iowa, Iowa City 52242.
Ramirez
L M
LM
Waldschmidt
T J
TJ
D000818:Animals; D001323:Autoantibodies / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D007136:Immunoglobulins / Q000276:immunology*; D015847:Interleukin-4 / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008811:Mice, Inbred DBA; D017455:Receptors, IgE / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*; D013154:Spleen / Q000166:cytology
D001323:Autoantibodies; D000949:Histocompatibility Antigens Class II; D007136:Immunoglobulins; D017455:Receptors, IgE; D015847:Interleukin-4