Human Extrafollicular CD4+ T Helper Cells Help Memory B Cells Produce Immunoglobulins

Follicular helper T (Tfh) cells are necessary for germinal center B cell maturation during primary immune responses; however, the T cells that promote humoral recall responses via memory B cells are less well defined. We herein characterize a human tonsillar CD4+ T cell subset with this function. These cells are similar to Tfh cells in terms of expression of the chemokine receptor CXCR5 and the inhibitory receptor PD-1, interleukin (IL)-21 secretion, and expression of the transcription factor BCL6; however, unlike Tfh cells that are located within the B cell follicle and germinal center, they reside at the border of the T cell zone and the B cell follicle in proximity to memory B cells, a position dictated by their unique chemokine receptor expression. They promote memory B cells to produce antibodies via CD40 ligand, IL-10, and IL-21. Our results reveal a unique extrafollicular CD4+ T cell subset in human tonsils, which specialize in promoting T cell-dependent humoral recall responses. We sorted four different CD4 T cell subgroups and extracted mRNA from each subgroup. The four subgroups are CD45RA+ T cells, T effector memory cells, T follicular helper cells and PSGL-1 high PD-1 high CXCR5 high T cells. The samples were obtained from three separate tonsils, and triplicates were made for the last two subgroups per each tonsil, generating a total of nine replicates for the last two subgroups.