Memory Phenotype Tfh Cells Are Homeostatically Maintained and Are Important for the Development of Germinal Centers and B Cell Responses to Virus Infection

Memory phenotype (MP) CD4 T cells that develop in the absence of overt antigen stimulation are important for both innate and adaptive immune responses. Although pathogen specific MP CD4 T cells have been found to function effectively against infection, it is not known if MP Tfh cells can also be developed in the absence of overt antigen stimulation. Here, we demonstrate that MP Tfh cells develop in the absence of overt antigen stimulation. In addition to FR4+, a mark found in pathogen induced memory Tfh cells, MP Tfh expressed high levels of Egr2. The development of MP Tfh are defective in CD2-Egr2/3−/− mice. MP Tfh cells share similar features in phenotypes and epigenetics with antigen induced memory Tfh cells and can effectively induce germinal center formation and B cells responses. Thus, MP Tfh cells regulated by Egr2/3 pathway are important component of adaptive immunity. Medical Research Council UK (MR/N00096X/1), Barts Charity (MGU0463)