CD4 ⁺ T Follicular Helper Cells in Human Tonsils and Blood Are Clonally Convergent but Divergent from Non-Tfh CD4 ⁺ Cells

Abstract

T follicular helper (Tfh) cells are fundamental for B cell selection and antibody maturation in germinal centers. Circulating Tfh (cTfh) cells constitute a minor proportion of the CD4 ⁺ T cells in peripheral blood, but their clonotypic relationship to Tfh populations resident in lymph nodes and the extent to which they differ from non-Tfh CD4 ⁺ cells have been unclear. Using donor-matched blood and tonsil samples, we investigate T cell receptor (TCR) sharing between tonsillar Tfh cells and peripheral Tfh and non-Tfh cell populations. TCR transcript sequencing reveals considerable clonal overlap between peripheral and tonsillar Tfh cell subsets as well as a clear distinction between Tfh and non-Tfh cells. Furthermore, influenza-specific cTfh cell clones derived from blood can be found in the repertoire of tonsillar Tfh cells. Therefore, human blood samples can be used to gain insight into the specificity of Tfh responses occurring in lymphoid tissues, provided that cTfh subsets are studied.

Graphical Abstract

In Brief

CD4 ⁺ T follicular helper (Tfh) cells are fundamental for antibody production. Brenna et al. demonstrate extensive repertoire overlap between Tfh populations in human blood and tonsils, whereas non-Tfh repertoires differ profoundly. Therefore, analysis of Tfh but not of total circulating CD4 ⁺ T cells can reflect the specificity of lymphoid tissue Tfh cells.