1. Negative selection of immature B cells by receptor editing or deletion is determined by site of antigen encounter.
- Author
-
Sandel PC and Monroe JG
- Subjects
- Animals, Antibodies, Blocking pharmacology, Antigens physiology, B-Lymphocytes cytology, Bone Marrow Cells immunology, Caspase 3, Caspases physiology, Cell Communication immunology, Cell Death immunology, Cell Differentiation immunology, Coculture Techniques, DNA-Binding Proteins biosynthesis, Gene Rearrangement, B-Lymphocyte, Mice, Mice, Inbred BALB C, Receptors, Antigen, B-Cell immunology, Receptors, Antigen, B-Cell physiology, Spleen immunology, Thy-1 Antigens analysis, Antigens immunology, B-Lymphocytes immunology, B-Lymphocytes metabolism, Clonal Deletion immunology, Receptors, Antigen, B-Cell metabolism
- Abstract
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.
- Published
- 1999
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