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

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

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

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 languageEnglish (US)
Article numbere2220120120
JournalProceedings of the National Academy of Sciences of the United States of America
Volume120
Issue number9
DOIs
StatePublished - Feb 28 2023

Bibliographical note

Funding Information:
We thank J. Ding and L. Qian for technical assistance, J. Motl from the University Flow Cytometry Resource for cell sorting, J. Moon for providing tetramer reagents, the University of Minnesota Genomics Center for assistance with RNA-seq, scRNA-seq and TCR analysis and the University of Minnesota Research Animal Resources for animal husbandry. The scRNA seq data reported here were previously described in the thesis work of O.C.S. Matous Voboril is a Cancer Research Institute Irvington Fellow supported by the Cancer Research Institute (CRI Award # CRI4536). This project was supported by the NIH (grant nos. R37 AI39560 and P01 AI35296 to K.A.H., T32 AI007313 to K.M.A. and E.R.B., and F30 AI131483 and T32 GM008244 to E.R.B.).

Funding Information:
seq data reported here were previously described in the thesis work of O.C.S. Matous Voboril is a Cancer Research Institute Irvington Fellow supported by the Cancer Research Institute (CRI Award # CRI4536). This project was supported by the NIH (grant nos. R37 AI39560 and P01 AI35296 to K.A.H., T32 AI007313 to K.M.A. and E.R.B., and F30 AI131483 and T32 GM008244 to E.R.B.).

Publisher Copyright:
Copyright © 2023 the Author(s). Published by PNAS.

Keywords

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

PubMed: MeSH publication types

  • Journal Article
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

Fingerprint

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