Type III interferon drives thymic B cell activation and regulatory T cell generation

Ryan J. Martinez, Elise R. Breed, Yosan Worota, Katherine M. Ashby, Matouš Vobořil, Tailor Mathes, Oscar C. Salgado, Christine H. O’Connor, Sergei V. Kotenko, Kristin A. Hogquist

Research output: Contribution to journalArticlepeer-review


The activation of thymic B cells is critical for their licensing as antigen presenting cells and resulting ability to mediate T cell central tolerance. The processes leading to licensing are still not fully understood. By comparing thymic B cells to activated Peyer’s patch B cells at steady state, we found that thymic B cell activation starts during the neonatal period and is characterized by TCR/CD40-dependent activation, followed by immunoglobulin class switch recombination (CSR) without forming germinal centers. Transcriptional analysis also demonstrated a strong interferon signature, which was not apparent in the periphery. Thymic B cell activation and CSR were primarily dependent on type III IFN signaling, and loss of type III IFN receptor in thymic B cells resulted in reduced thymocyte regulatory T cell (Treg) development. Finally, from TCR deep sequencing, we estimate that licensed B cells induce development of a substantial fraction of the Treg cell repertoire. Together, these findings reveal the importance of steady-state type III IFN in generating licensed thymic B cells that induce T cell tolerance to activated B cells.

Original languageAmerican English
Article numbere2220120120
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number9
StatePublished - Feb 28 2023
Externally publishedYes

ASJC Scopus subject areas

  • General


  • T cell selection
  • central tolerance
  • thymic B cells
  • type III IFN


Dive into the research topics of 'Type III interferon drives thymic B cell activation and regulatory T cell generation'. Together they form a unique fingerprint.

Cite this