NFKB2 regulates human Tfh and Tfr pool formation and germinal center potential

Pasqualina De Leo, Luisa Gazzurelli, Manuela Baronio, Davide Montin, Silvia Di Cesare, Carmen Giancotta, Francesco Licciardi, Caterina Cancrini, Alessandro Aiuti, Alessandro Plebani, Maria Pia Cicalese, Vassilios Lougaris, Georgia Fousteri

Research output: Contribution to journalArticle

Abstract

Mutations affecting the non-canonical pathway of NF-κB were recently identified to underlie a form of common variable immunodeficiency strongly associated with autoimmunity. Although intrinsic B-cell abnormalities explain most of the humoral defects of this disease, detailed data on the impact of NFKB2 on follicular helper (Tfh) and regulatory (Tregs) T cells are scarce. Here, we show that Tfh, CXCR5+, and CXCR5- Treg cell subsets were significantly reduced in patients heterozygous for a truncating mutation of NFKB2. Plasma CXCL13 levels were reduced, underlining an important role for NFKB2 in regulating the germinal center (GC) response. Proinflammatory IFNγ, IL-17 and IL-10 cytokine production by CD4 T cells was lower in the mutated patients, but the production of IL-4 and IL-21 was not altered. Taken together, our findings show that NFKB2 influences the quality and efficiency of human GC reaction, by affecting not only the B cells but also GC-relevant T cell subsets.

Original languageEnglish
Pages (from-to)108309
JournalClinical Immunology
Volume210
DOIs
Publication statusE-pub ahead of print - 2019

    Fingerprint

Cite this

De Leo, P., Gazzurelli, L., Baronio, M., Montin, D., Di Cesare, S., Giancotta, C., Licciardi, F., Cancrini, C., Aiuti, A., Plebani, A., Cicalese, M. P., Lougaris, V., & Fousteri, G. (2019). NFKB2 regulates human Tfh and Tfr pool formation and germinal center potential. Clinical Immunology, 210, 108309. https://doi.org/10.1016/j.clim.2019.108309