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

Jason Perera1, Zhong Zheng2, Shuyin Li2

  • 1Committee on Immunology, University of Chicago, Chicago, IL 60637, USA; Department of Medicine, Section of Rheumatology, and Knapp Center for Lupus and Immunology Research, University of Chicago, Chicago, IL 60637, USA.

Cell Reports
|October 6, 2016
PubMed
Summary

Thymic B cells undergo class switching through T cell interactions, expanding autoreactive B cells. These class-switched B cells are crucial for maintaining CD4 T cell tolerance.

Keywords:
B cell class switchingT cell negative selectionantigen presentationautoreactive B cellautoreactive T cellself-antigenthymic B cellstolerance

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Area of Science:

  • Immunology
  • Cell Biology
  • T cell development

Background:

  • B cells function as antigen-presenting cells, linking B cell receptor signaling to antigen presentation.
  • Autoreactive thymic B cells present self-antigens, influencing CD4+ T cell negative selection.
  • The interplay between thymic B cells and thymocytes, and its impact on repertoire selection, remains unclear.

Purpose of the Study:

  • To investigate the intrathymic B cell repertoire and its interaction with T cells.
  • To understand the mechanisms driving B cell class switching within the thymus.
  • To determine the role of class-switched thymic B cells in T cell tolerance.

Main Methods:

  • Analysis of B cell class switching within the thymus.
  • Investigating the requirement of T cell interaction for B cell class switching.
  • Comparative repertoire analysis of thymic B cells (switched vs. unswitched) and splenic B cells.

Main Results:

  • A significant proportion of thymic B cells exhibit intrathymic class switching.
  • Cognate T cell interaction is essential for thymic B cell class switching.
  • Class-switched thymic B cells possess a distinct repertoire compared to unswitched thymic or splenic B cells.
  • Autoreactive B cell specificities are preferentially expanded in the thymus via class switching.

Conclusions:

  • Intrathymic B cell class switching, dependent on T cell interaction, shapes the B cell repertoire.
  • Enriched, class-switched autoreactive thymic B cells are key players in establishing CD4 T cell tolerance.