Clonal anergy of memory B cells in epitope-specific regulation.
Immunization of carrier (keyhole limpet hemocyanin (KLH)) primed mice with the hapten-carrier TNP-KLH induces specific suppression for the IgG anti-TNP-response without interfering with the response to epitopes on the carrier molecule. To examine the status of hapten-specific memory B cells from suppressed mice, highly enriched populations of TNP-specific memory B cells were purified from the spleen of TNP-KLH (control) or KLH/TNP-KLH (suppressed) immunized mice and tested in vitro for their ability to respond to TD or TI (TNP-KLH, TNP-LPS) antigenic challenge in presence of a KLH-specific Th cell line. Similar numbers of TNP-specific B cells with the characteristics of memory B cells were obtained from control and suppressed mice. TNP-specific B cells from suppressed mice could be triggered to IgG production by TNP-LPS but had an impaired ability to differentiate into IgG-secreting cells in response to TNP-KLH. This impaired IgG response to TNP-KLH was not due to an active suppression by a subset of TNP-specific B cells, or to an impedence of memory cells to a class switching but to an intrinsic memory B cell defect. TNP-specific B cells from suppressed mice were as efficient as memory B cells from control mice to present TNP-KLH to KLH-specific Th cells and to proliferate in response to T cell help. Our data support the view that the effector mechanism of epitope specific regulation does not interfere with the development of hapten-specific memory B cells but that these cells have an intrinsic defect that prevents their differentiation into active IgG antibody secreting cells in response to a T-dependent antigenic challenge.
CNRS URA-359, Institut Pasteur, Laboratory of Biologie des Régulations Immunitaires, Paris, France.
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A
Galelli
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Charlot
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation; D000939:Epitopes; D006241:Haptens; D006433:Hemocyanins / Q000276:immunology; D007074:Immunoglobulin G / Q000096:biosynthesis; D007156:Immunologic Memory; D007165:Immunosuppression Therapy; D008213:Lymphocyte Activation; D051379:Mice; D008811:Mice, Inbred DBA; D013154:Spleen / Q000166:cytology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D014301:Trinitrobenzenes / Q000276:immunology
D000939:Epitopes; D006241:Haptens; D007074:Immunoglobulin G; D014301:Trinitrobenzenes; D006433:Hemocyanins