[PDF][PDF] Negative selection of immature B cells by receptor editing or deletion is determined by site of antigen encounter

PC Sandel, JG Monroe - Immunity, 1999 - cell.com
PC Sandel, JG Monroe
Immunity, 1999cell.com
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 …
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.
cell.com