Enforced Bcl-2 expression inhibits antigen-mediated clonal elimination of peripheral B cells in an antigen dose-dependent manner and promotes receptor editing in autoreactive, immature B cells
- Author(s)
- Lang, J; Arnold, B; Hammerling, G; Harris, AW; Korsmeyer, S; Russell, D; Strasser, A; Nemazee, D;
- Details
- Publication Year 1997-11-03,Volume 186,Issue #9,Page 1513-1522
- Journal Title
- JOURNAL OF EXPERIMENTAL MEDICINE
- Publication Type
- Journal Article
- Abstract
- The mechanisms that establish immune tolerance in immature and mature B cells appear to be distinct. Membrane-bound autoantigen is thought to induce developmental al-rest and receptor editing in immature B cells, whereas mature B cells have shortened lifespans when exposed to the same stimulus. In this study, we used E mu-bcl-2-22 transgenic (Tg) mice to test the prediction that enforced expression of the Bcl-2 apoptotic inhibitor in B cells would rescue mature, but not immature, B cells from tolerance induction. To monitor tolerance to the natural membrane autoantigen H-2K(b), we bred 3-83 mu delta (anti-K-k,K-b) Ig Tg mice to H-2(b) mice or to mice expressing transgene-driven K-b in the periphery. In 3-83 mu delta/bcl-2 Tg mice, deletion of autoreactive B cells induced by peripheral K-b antigen expression in the liver (MT-K-b Tg) or epithelia (KerIV-K-b Tg), was partly or completely inhibited, respectively. Furthermore, Bcl-2 protected peritoneal B-2 B cells from deletion mediated by acute antigen exposure, but this protection could be overcome by higher antigen dose. In contrast to its ability to block peripheral self-tolerance, Bcl-2 overexpression failed to inhibit central tolerance induced by bone marrow antigen expression, but instead, enhanced the receptor editing process. These studies indicate that apoptosis plays distinct roles in central and peripheral B cell tolerance.
- Publisher
- ROCKEFELLER UNIV PRESS
- Keywords
- TOLERANCE
- Publisher's Version
- https://doi.org/10.1084/jem.186.9.1513
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 1997-11-03 12:00:00