ELIMINATION OF SELF-REACTIVE LYMPHOCYTES-B PROCEEDS IN 2 STAGES - ARRESTED DEVELOPMENT AND CELL-DEATH
- Author(s)
- HARTLEY, SB; COOKE, MP; FULCHER, DA; Harris, AW; Cory, S; Basten, A; Goodnow, CC;
- Details
- Publication Year 1993-02-12,Volume 72,Issue #3,Page 325-335
- Journal Title
- CELL
- Publication Type
- Journal Article
- Abstract
- In transgenic mice, self-reactive B lymphocytes are eliminated if they encounter membrane-bound self antigens during their development within the bone marrow. We show here that two separate and sequential events, arrested development and cell death, bring about B cell elimination. Developmental arrest is an early outcome of antigen binding in immature B cells, blocks acquisition of adhesion molecules and receptors important for B cell migration and activation, and is rapidly reversible by removal of antigen. Death of the arrested B cells occurs within 1 to 3 days and can be delayed by expression of a bcl-2 transgene, which results in escape of large numbers of self-reactive B cells from the bone marrow but fails to override the developmental arrest. These findings define a novel pathway for B cell elimination, involving an initial stage vulnerable to breakdown in autoimmune disease.
- Publisher
- CELL PRESS
- Keywords
- COMPLEMENT RECEPTOR TYPE-2; IMMUNOGLOBULIN MU-CHAIN; MOUSE BONE-MARROW; TRANSGENIC MICE; CLONAL DELETION; ANTIBODY-RESPONSES; T-CELLS; EXPRESSION; TOLERANCE; DIFFERENTIATION
- Publisher's Version
- https://doi.org/10.1016/0092-8674(93)90111-3
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 1993-02-12 12:00:00