Notch2-dependent DC2s mediate splenic germinal center responses

Carlos G. Briseño, Ansuman T. Satpathy, Jesse T. Davidson, Stephen T. Ferris, Vivek Durai, Prachi Bagadia, Kevin W. O'Connor, Derek J. Theisen, Theresa L. Murphy, Kenneth M. Murphy

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

Abstract

CD4+ T follicular helper (TFH) cells support germinal center (GC) reactions promoting humoral immunity. Dendritic cell (DC) diversification into genetically distinct subsets allows for specialization in promoting responses against several types of pathogens. Whether any classical DC (cDC) subset is required for humoral immunity is unknown, however. We tested several genetic models that selectively ablate distinct DC subsets in mice for their impact on splenic GC reactions. We identified a requirement for Notch2-dependent cDC2s, but not Batf3-dependent cDC1s or Klf4-dependent cDC2s, in promoting TFH and GC B cell formation in response to sheep red blood cells and inactivated Listeria monocytogenes. This effect was mediated independent of Il2ra and several Notch2-dependent genes expressed in cDC2s, including Stat4 and Havcr2. Notch2 signaling during cDC2 development also substantially reduced the efficiency of cDC2s for presentation ofMHC class II-restricted antigens, limiting the strength of CD4 T cell activation. Together, these results demonstrate a nonredundant role for the Notch2-dependent cDC2 subset in supporting humoral immune responses.

Original languageEnglish
Pages (from-to)10726-10731
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume115
Issue number42
DOIs
StatePublished - Oct 16 2018

Keywords

  • Dendritic cell
  • Germinal center
  • T follicular helper cell

Fingerprint

Dive into the research topics of 'Notch2-dependent DC2s mediate splenic germinal center responses'. Together they form a unique fingerprint.

Cite this