Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 115, Issue 38, Pages 9604-9609Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1808594115
Keywords
diversity; autoimmunity; stochasticity; TCR; follicular
Categories
Funding
- LabEx Transimmunom [ANR-11-IDEX-0004-02]
- European Research Council-Advanced Grant [322856]
- Recherche Hospitalo-Universitaire Grant [ANR 16-RHUS-0001]
- Russian Science Foundation Grant [17-15-01495]
- European Research Council (ERC) [322856] Funding Source: European Research Council (ERC)
- Russian Science Foundation [17-15-01495] Funding Source: Russian Science Foundation
- Agence Nationale de la Recherche (ANR) [ANR-16-RHUS-0001] Funding Source: Agence Nationale de la Recherche (ANR)
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T follicular helper (Tfh) and regulatory (Tfr) cells are terminally differentiated cells found in germinal centers (GCs), specialized secondary lymphoid organ structures dedicated to antibody production. As such, follicular T (Tfol) cells are supposed to be specific for immunizing antigens, which has been reported for Tfh cells but is debated for Tfr cells. Here, we used high-throughput T cell receptor (TCR) sequencing to analyze the repertoires of Tfh and Tfr cells, at homeostasis and after immunization with self-or foreign antigens. We observed that, whatever the conditions, Tfh and Tfr cell repertoires are less diverse than those of effector T cells and Treg cells of the same tissues; surprisingly, these repertoires still represent thousands of different sequences, even after immunization with a single antigen that induces a 10-fold increase in Tfol cell numbers. Thorough analysis of the sharing and network of TCR sequences revealed that a specific response to the immunizing antigen can only, but hardly, be detected in Tfh cells immunized with a foreign antigen and Tfr cells immunized with a self-antigen. These antigen-specific responses are obscured by a global stimulation of Tfh and Tfr cells that appears to be antigen-independent. Altogether, our results suggest a major bystander Tfol cell activation during the immune response in the GCs.
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