Journal
JOURNAL OF EXPERIMENTAL MEDICINE
Volume 210, Issue 1, Pages 125-142Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20120525
Keywords
-
Categories
Funding
- National Institutes of Health [RO1AI76585-01, U19AI082724-02]
- Arthritis Foundation
- Lupus Research Institute
Ask authors/readers for more resources
The important subtleties of B cell tolerance are best understood in a diverse immunoglobulin (Ig) repertoire context encoding a full spectrum of autoreactivity. To achieve this, we used mice expressing Ig. transgenes that confer varying degrees of autoreactivity within a diverse heavy chain (HC) repertoire. These transgenes, coupled with a biomarker to identify receptor-edited cells and combined with expression cloning of B cell receptors, allowed us to analyze tolerance throughout B cell development. We found that both the nature of the autoantigen and the Ig HC versus light chain (LC) contribution to autoreactivity dictate the developmental stage and mechanism of tolerance. Furthermore, although selection begins in the bone marrow, over one third of primary tolerance occurs in the periphery at the late transitional developmental stage. Notably, we demonstrate that the LC has profound effects on tolerance and can lead to exacerbated autoantibody production.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available