High-resolution repertoire analysis reveals a major bystander activation of Tfh and Tfr cells
PG Ritvo, A Saadawi, P Barennes… - Proceedings of the …, 2018 - National Acad Sciences
PG Ritvo, A Saadawi, P Barennes, V Quiniou, W Chaara, K El Soufi, B Bonnet, A Six…
Proceedings of the National Academy of Sciences, 2018•National Acad SciencesT 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 …
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 …
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.
National Acad Sciences