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Proc Natl Acad Sci U S A. 2018 Oct 16;115(42):10726-10731. doi: 10.1073/pnas.1809925115. Epub 2018 Oct 2.

Notch2-dependent DC2s mediate splenic germinal center responses.

Author information

1
Department of Pathology and Immunology, Washington University School of Medicine in St. Louis, St. Louis, MO 63110.
2
Center for Personal Dynamic Regulomes, Stanford University School of Medicine, Stanford, CA 94305.
3
Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305.
4
Department of Pathology and Immunology, Washington University School of Medicine in St. Louis, St. Louis, MO 63110; kmurphy@wustl.edu.
5
Howard Hughes Medical Institute, Washington University School of Medicine in St. Louis, St. Louis, MO 63110.

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 of MHC 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.

KEYWORDS:

T follicular helper cell; dendritic cell; germinal center

PMID:
30279176
PMCID:
PMC6196531
DOI:
10.1073/pnas.1809925115
[Indexed for MEDLINE]
Free PMC Article

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