Assembly of a spatial circuit of T-bet-expressing T and B lymphocytes is required for antiviral humoral immunity Journal Article


Authors: Mendoza, A.; Yewdell, W. T.; Hoyos, B.; Schizas, M.; Bou-Puerto, R.; Michaels, A. J.; Brown, C. C.; Chaudhuri, J.; Rudensky, A. Y.
Article Title: Assembly of a spatial circuit of T-bet-expressing T and B lymphocytes is required for antiviral humoral immunity
Abstract: Effective antiviral immunity requires generation of T and B lymphocytes expressing the transcription factor T-bet, a regulator of type 1 inflammatory responses. Using T-bet expression as an endogenous marker for cells participating in a type 1 response, we report coordinated interactions of T-bet-expressing T and B lymphocytes on the basis of their dynamic colocalization at the T cell zone and B follicle boundary (T-B boundary) and germinal centers (GCs) during lung influenza infection. We demonstrate that the assembly of this circuit takes place in distinct anatomical niches within the draining lymph node, guided by CXCR3 that enables positioning of TH1 cells at the T-B boundary. The encounter of B and TH1 cells at the T-B boundary enables IFN-? produced by the latter to induce IgG2c class switching. Within GCs, T-bet+TFHcells represent a specialized stable sublineage required for GC growth but dispensable for IgG2c class switching. Our studies show that during respiratory viral infection, T-bet- expressing T and B lymphocytes form a circuit assembled in a spatiotemporally controlled manner that acts as a functional unit enabling a robust and coherent humoral response tailored for optimal antiviral immunity. © 2021 American Association for the Advancement of Science. All rights reserved.
Journal Title: Science Immunology
Volume: 6
Issue: 60
ISSN: 2470-9468
Publisher: Amer Assoc Advancement Science  
Date Published: 2021-06-01
Start Page: eabi4710
Language: English
DOI: 10.1126/sciimmunol.abi4710
PUBMED: 34117110
PROVIDER: scopus
PMCID: PMC8418793
DOI/URL:
Notes: Article -- Export Date: 1 July 2021 -- Source: Scopus
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MSK Authors
  1. Beatrice E Hoyos
    23 Hoyos
  2. Alexander Rudensky
    156 Rudensky
  3. Michail Schizas
    27 Schizas
  4. William Theodore Yewdell
    17 Yewdell
  5. Chrysothemis Celia Margaret Brown
    18 Brown