Self-Antigen-Driven Thymic B Cell Class Switching Promotes T Cell Central Tolerance

Jason Perera, Zhong Zheng, Shuyin Li, Herman Gudjonson, Olga Kalinina, Jennifer I.C. Benichou, Katharine E. Block, Yoram Louzoun, Dengping Yin, Anita S. Chong, Aaron R. Dinner, Martin Weigert, Haochu Huang

Research output: Contribution to journalArticlepeer-review

Abstract

B cells are unique antigen-presenting cells because their antigen presentation machinery is closely tied to the B cell receptor. Autoreactive thymic B cells can efficiently present cognate self-antigens to mediate CD4+ T cell-negative selection. However, the nature of thymocyte-thymic B cell interaction and how this interaction affects the selection of thymic B cell repertoire and, in turn, the T cell repertoire are not well understood. Here we demonstrate that a large percentage of thymic B cells have undergone class switching intrathymically. Thymic B cell class switching requires cognate interaction with specific T cells. Class-switched thymic B cells have a distinct repertoire compared with unswitched thymic B cells or splenic B cells. Particularly, autoreactive B cell specificities preferentially expand in the thymus by undergoing class switching, and these enriched, class-switched autoreactive thymic B cells play an important role in CD4 T cell tolerance.

Original languageEnglish (US)
Pages (from-to)387-398
Number of pages12
JournalCell reports
Volume17
Issue number2
DOIs
StatePublished - Oct 4 2016
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2016 The Authors

Keywords

  • B cell class switching
  • T cell negative selection
  • antigen presentation
  • autoreactive B cell
  • autoreactive T cell
  • self-antigen
  • thymic B cells
  • tolerance

Fingerprint

Dive into the research topics of 'Self-Antigen-Driven Thymic B Cell Class Switching Promotes T Cell Central Tolerance'. Together they form a unique fingerprint.

Cite this