Fig. P1.

Two distinct Tfh-committed cells in human tonsils differentially help B-cell subsets. CXCR5^loICOS^lo CD4⁺ T cells localize exclusively outside germinal centers (GC) and induce naïve and memory B cells to become antibody-secreting cells. CXCR5^hiICOS^hi GC-Tfh cells are specialized to help B cells in GCs. Whereas CXCR5^loICOS^lo CD4⁺ T cells produce higher levels of IL-21 upon interaction with B cells, GC-Tfh cells produce higher levels of CXCL13. CXCR5^loICOS^lo CD4⁺ T cells and GC-Tfh cells show similar expression profiles of BCL6 and PRDM1 transcripts. Our study suggests that tonsillar CXCR5^loICOS^lo CD4⁺ T cells represent Tfh-committed extrafollicular helper cells and/or precursors of GC-Tfh cells.