Evolution of antigen-specific follicular helper T cell transcriptional programs across effector function and through to memory

Understanding how follicular helper T cells (TFH) regulate the specialization, maturation, and differentiation of adaptive B cell immunity is crucial for developing durable high-affinity immune protection. Using indexed-single cell molecular strategies, we reveal a skewed intra-clonal assortment of higher affinity TCR and the distinct molecular programming of the localized TFH compartment compared to emigrant conventional effector TH (ETH) cells. We find a temporal shift in BCR class switch which permits identification of inflammatory and anti-inflammatory modules of transcriptional programming that subspecialize TFH function before and during the germinal center (GC) reaction. Late collapse of this local primary GC reaction reveals a persistent post-GC TFH population which discloses a putative memory TFH program. These studies define specialized antigen-specific TFH transcriptional programs that progressively direct class-specific evolution of high-affinity B cell immunity and uncover the transcriptional program of a memory TFH population as the regulators of antigen recall. ![Figure][1] Summary Distinct inflammatory and anti-inflammatory antigen-specific TFH transcriptional programs regulate class-specific B cell maturation. Highlights ### Competing Interest Statement The authors have declared no competing interest. [1]: pending:yes