Negative selection of immature B cells by receptor editing or deletion is determined by site of antigen encounter.
Immature B cells that encounter self-antigen are eliminated from the immune repertoire by negative selection. Negative selection has been proposed to take place by two distinct mechanisms: deletion by apoptosis or alteration of the antigen receptor specificity by receptor editing. While convincing evidence exists for each, the two models are inherently contradictory. In this paper, we propose a resolution to this contradiction by demonstrating that the site of first antigen encounter dictates which mechanism of negative selection is utilized. We demonstrate that the bone marrow microenvironment provides signals that block antigen-induced deletion and promote RAG reinduction. In the periphery, the absence of these signals allows the immature B cell to default to apoptosis as a result of BCR engagement.
Sandel
P C
PC
Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia 19104, USA.
Monroe
J G
JG
D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D000941:Antigens / Q000276:immunology* / Q000502:physiology; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D001854:Bone Marrow Cells / Q000276:immunology; D053148:Caspase 3; D020169:Caspases / Q000502:physiology; D002450:Cell Communication / Q000276:immunology; D016923:Cell Death / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D017637:Clonal Deletion / Q000276:immunology*; D018920:Coculture Techniques; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D015322:Gene Rearrangement, B-Lymphocyte; D051379:Mice; D008807:Mice, Inbred BALB C; D011947:Receptors, Antigen, B-Cell / Q000276:immunology / Q000378:metabolism* / Q000502:physiology; D013154:Spleen / Q000276:immunology; D018800:Thy-1 Antigens / Q000032:analysis
D019138:Antibodies, Blocking; D000941:Antigens; D004268:DNA-Binding Proteins; C499308:Rag2 protein, mouse; D011947:Receptors, Antigen, B-Cell; D018800:Thy-1 Antigens; C064655:V(D)J recombination activating protein 2; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases