MiR-17~92 family microRNAs are critical regulators of T follicular helper cell differentiation (P1133)

Abstract

Abstract Germinal center (GC) reaction is a key event in B cell-mediated immune responses and CD4+ T cell help plays an essential role in these process. A distinct CD4+ effector T cell subset, T follicular helper cells (TFH), provides this help to B cells. However, molecular mechanisms underlying TFH differentiation are still largely unknown. A recent study revealed that Bcl-6 is a signature transcription factor regulating TFH differentiation and it represses the expression of miR-17~92 in CD4+ T cells. MiR-17~92 in turn suppresses the expression of CXCR5, a critical chemokine receptor controlling CD4+ T cell migration into B cell follicles. The authors therefore concluded that miR-17~92 functions as a negative regulator of TFH differentiation. Here we report the surprising finding that mice with miR-17~92 family microRNAs (miRNAs) deleted specifically in T cells exhibited severely compromised TFH differentiation, germinal center formation, and reduced antibody responses upon protein antigen immunization. Those mutant mice were also defective in TFH differentiation and germinal center B (GCB) cell formation during lymphocytic choriomeningitis virus (LCMV) clone-13 infection and failed to control the virus. Conversely, T cell-specific miR-17~92 transgenic mice spontaneously accumulated TFH cells. Novel cellular and molecular mechanisms underlying miR-17~92 family miRNA-mediated regulation of TFH differentiation will be presented at this meeting.