B cell tolerance and autoimmunity: Lessons from repertoires.

The Journal of experimental medicine
Authors
Abstract

Adaptive immune cell function is regulated by a highly diverse receptor recombined from variable germline-encoded segments that can recognize an almost unlimited array of epitopes. While this diversity enables the recognition of any pathogen, it also poses a risk of self-recognition, leading to autoimmunity. Many layers of regulation are present during both the generation and activation of B cells to prevent this phenomenon, although they are evidently imperfect. In recent years, our ability to analyze immune repertoires at scale has drastically increased, both through advances in sequencing and single-cell analyses. Here, we review the current knowledge on B cell repertoire analyses, focusing on their implication for autoimmunity. These studies demonstrate that a failure of tolerance occurs at multiple independent checkpoints in different autoimmune contexts, particularly during B cell maturation, plasmablast differentiation, and within germinal centers. These failures are marked by distinct repertoire features that may be used to identify disease- or patient-specific therapeutic approaches.

Year of Publication
2024
Journal
The Journal of experimental medicine
Volume
221
Issue
9
Date Published
09/2024
ISSN
1540-9538
DOI
10.1084/jem.20231314
PubMed ID
39093312
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