Strength of signal through BCR determines the fate of cycling B cells by regulating the expression of the Bcl-2 family of survival proteins.
Cycling, splenic B cells were recultured with: (1) no stimulant to reflect poorly competitive clones; (2) soluble, whole anti-mu to reflect clones that bind soluble immune complexes; (3) soluble F(ab')2 anti-mu to reflect clones that bind soluble antigen; and (4) immobilized anti-mu to reflect clones that bind antigen presented by FDC. All four groups displayed similar levels of the death proteins Bax and Bcl-xS. In contrast, cycling B cells restimulated with either soluble F(ab')2 or immobilized anti-mu expressed heightened levels of the survival protein Bcl-xL, and only cells restimulated with immobilized anti-mu expressed the survival protein Bcl-2. Cycling B cells restimulated with either soluble F(ab')2 or immobilized anti-mu displayed a selective survival advantage over cycling B cells receiving no stimulus or soluble, whole anti-mu by both enhancing their responsiveness to CD40 ligand, a Th-cell-derived signal, and increasing the period that the cycling B cells remained responsive to this Th-cell-derived signal. The Th-cell-derived signal did not appreciably alter cycling B cell expression of Bcl-2 family members.
Pittner
B T
BT
Department of Microbiology and Immunology, University of Kentucky Medical Center, Lexington 40536-0084, USA.
Snow
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EC
D000818:Animals; D017209:Apoptosis; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D023201:CD40 Ligand; D002453:Cell Cycle; D002454:Cell Differentiation; D002460:Cell Line; D002478:Cells, Cultured; D005260:Female; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology; D051379:Mice; D008811:Mice, Inbred DBA; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis*; D011817:Rabbits; D011947:Receptors, Antigen, B-Cell / Q000276:immunology*; D015398:Signal Transduction; D018411:Spodoptera; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D019014:fas Receptor / Q000276:immunology
C494827:Bax protein, mouse; C494812:Bcl2l1 protein, mouse; D008562:Membrane Glycoproteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011947:Receptors, Antigen, B-Cell; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D019014:fas Receptor; D023201:CD40 Ligand