High-resolution repertoire analysis reveals a major bystander activation of Tfh and Tfr cells - Sorbonne Université Access content directly
Journal Articles Proceedings of the National Academy of Sciences of the United States of America Year : 2018

High-resolution repertoire analysis reveals a major bystander activation of Tfh and Tfr cells

Abstract

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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hal-03867773 , version 1 (24-02-2023)

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Paul-Gydeon Ritvo, Ahmed Saadawi, Pierre Barennes, Valentin Quiniou, Wahiba Chaara, et al.. High-resolution repertoire analysis reveals a major bystander activation of Tfh and Tfr cells. Proceedings of the National Academy of Sciences of the United States of America, 2018, 115 (38), pp.9604-9609. ⟨10.1073/pnas.1808594115⟩. ⟨hal-03867773⟩
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