Tolerant B lymphocytes acquire resistance to Fas-mediated apoptosis after treatment with interleukin 4 but not after treatment with specific antigen unless a surface immunoglobulin threshold is exceeded.
Susceptibility to Fas-mediated apoptosis in nontolerant B cells is regulated in a receptor-specific fashion. To explore the regulation of Fas killing in tolerant, autoreactive B cells, mice doubly transgenic for hen egg lysozyme (HEL)-specific B cell receptors and soluble HEL were examined. Engagement of CD40 led to enhanced Fas expression and acquisition of sensitivity to Fas-mediated apoptosis in tolerant B cells, similar to that observed in nontolerant, receptor transgenic B cells. Engagement of surface immunoglobulin by specific (HEL) antigen failed to induce Fas resistance in tolerant B cells, in contrast to its effect on nontolerant B cells; however, cross-linking of biotinylated HEL with streptavidin induced similar levels of Fas resistance in tolerant and nontolerant B cells, which approximated the degree of Fas resistance produced by anti-Ig. Unlike surface Ig (sIg) engagement, physiological engagement of IL-4 receptors produced similar levels of Fas resistance in tolerant and nontolerant B cells. Thus, tolerant B cells differ from nontolerant B cells in the diminished capacity of surface immunoglobulin engagement to produce Fas resistance; however, tolerant B cells can be induced to become resistant to Fas-mediated apoptosis by IL-4 or by higher order cross-linking of sIg receptors.
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Department of Microbiology, Boston University Medical Center, Boston, Massachusetts 02118, USA.
Marshak-Rothstein
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Rothstein
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D000818:Animals; D017209:Apoptosis; D001402:B-Lymphocytes / Q000276:immunology*; D023201:CD40 Ligand; D007108:Immune Tolerance; D015847:Interleukin-4 / Q000494:pharmacology*; D008297:Male; D008562:Membrane Glycoproteins / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009113:Muramidase / Q000276:immunology; D011947:Receptors, Antigen, B-Cell / Q000502:physiology*; D019014:fas Receptor / Q000502:physiology*
D008562:Membrane Glycoproteins; D011947:Receptors, Antigen, B-Cell; D019014:fas Receptor; D023201:CD40 Ligand; D015847:Interleukin-4; D009113:Muramidase