T cell immune response within B-cell follicles

B-cell follicle represents a functionally dynamic microstructure within second lymphoid tissues, predominantly consisting of B cells, follicular T cells and DCs. Through intimate interactions with cognate B cells, follicular helper T cells (Tfh) initiate and facilitate germinal center (GC) reactions by providing signals required for producing high-affinity antibodies, as well as for the generation of long-lived antibody-secreting plasma cells and memory B cells. Concomitantly, germinal center reaction needs to be fine controlled to avoid autoimmunity or B-cell malignancies. Among immune cells residing in follicles, follicular regulatory T cells (Tfr), converted from naïve Treg cells, are specifically assigned to repress excessive GC responses by suppressing Tfh and GC B cells within GC structure. Hence, through Yin and Yang (positive and negative) regulation of GC reaction, Tfh cells play concert with Tfr cells in maintaining immune homeostasis. Besides CD4⁺ T cells, a small portion of CXCR5 expressing CD8⁺ T cells, regarded as follicular cytotoxic T cells (Tfc), could migrate into B cell follicles during chronic viral infection and several types of cancers, and this population exhibit lower level of exhaustion than its CXCR5^- counterparts. Besides, Tfc cells demonstrate a stem-cell like phenotype during chronic infection which could further differentiate into terminally differentiated CXCR5^-CD8⁺ T cells. Collectively, in this review, we will discuss the recent advances in our understanding of the ontology and differentiation of B-cell follicle resident Tfh, Tfr and Tfc cells.