Chronic graft-versus-host reaction is associated with a decrease in Ig light chain receptor editing in bone marrow self-reactive B cells
✍ Scribed by Nili Feuerstein; Dennis C. DeSimone; Robert A. Eisenberg; Terri H. Finkel
- Publisher
- John Wiley and Sons
- Year
- 2004
- Tongue
- English
- Weight
- 243 KB
- Volume
- 34
- Category
- Article
- ISSN
- 0014-2980
No coin nor oath required. For personal study only.
✦ Synopsis
Abstract
The encounter of developing B cells in the bone marrow with soluble hen egg lysozyme (sHEL) self antigen induces anergy and endogenous κ light chain rearrangements (‘receptor editing’). We have previously shown that induction of chronic graft‐versus‐hostreaction (GVH) in tolerant Ig/sHEL mice results in prevention of B cell anergy in the bone marrow and the spleen. We now report that in chronic GVH, immature self‐reactive B cells also show reduced levels of receptor editing in the bone marrow. This is evidenced by the following observations: (a) a small population of‘receptor‐edited’ B cells, which is found in tolerant mice, is markedly reduced in mice that have lost tolerance in chronic GVH; (b) self‐reactive B cells in GVH mice have reduced levels of endogenous κ chain rearrangements; and (c) recombinase‐activating gene (RAG)‐2 expression is markedly decreased in immature self‐reactive B cells in the bone marrow of chronic GVH mice. These results suggest that in chronic GVH newly emerging B cells escape tolerance, in part because of decreased receptor editing in the bone marrow. Thus, the autoimmunity induced by chronic GVH may ultimately result from the failure of B cell tolerance at multiple checkpoints.