T‐cell subsets in the germinal center

Abstract

T cells are known to migrate to B-cell-enriched follicles and germinal centers within secondary lymphoid organs to provide help to B cells. Cognate T:B interactions that take place at the T:B border and subsequently within germinal centers are essential for B-cell priming, differentiation into germinal center B cells, and selection of mutated cells into memory B cells or memory plasma cells. In recent years, different stages of maturation within B-cell helper T cells, collectively known as B-follicular helper T (Tfh) cells, as well as heterogeneity amid germinal center T cells are becoming clear. Indeed, germinal centers support not only bona fide Tfh cells but also CD4(+) and CD8(+) follicular regulatory T (Tfr) cells that act to suppress germinal center responses and B-cell helper natural killer T cells. There is a growing need for more precise phenotypic and functional distinction of these specialized T-cell subsets. In this review, we summarize current knowledge on the ontogeny, molecular identity, and functional relevance of the various subsets of germinal center T cells.

T follicular helper expansion and humoral-mediated rejection are independent of the HVEM/BTLA pathway

“…IL-21, IL-4, and IL-6) and cell-bound molecules, such as ICOS (inducible T-cell co-stimulator) and CD40L that deliver costimulatory signals to ICOS-L and CD40 expressing alloantigen-specific B cells. 10 These interactions drive B-cell differentiation towards extrafollicular short-lived plasma blasts and intrafollicular long-lived plasma cells, which produce antibodies, as well as the formation of memory B cells. [10][11][12][13] The transcriptional repressor B-cell lymphoma 6 seems to regulate the genetic program of CD4Tfh cell differentiation and is a suitable biomarker that is useful in distinguishing these cells from other CD4 T cells (e.g.…”

CD4+ follicular helper T cell infiltration predicts breast cancer survival

“…While their role in antitumor immunity is unknown, studies of cellular interactions in secondary lymphoid organs show that Tfh cells are key players in the generation of T cell-dependent antibody responses and B cell memory (73). Collectively, these data (predominantly from animal models) demonstrate that these specialized Th cells are intimately involved in GC development and provide critical help for antigen-specific B cell maturation to high-affinity memory cells and long-lived plasma cells (28,43,74). While long considered minor players in antitumor immunity (75), plasma cells infiltrating non-small cell lung cancer (76) and CD20 + B cells infiltrating BC (77), ovarian cancer (78), melanoma (79), and colorectal carcinoma (80) have been associated with increased survival.…”

DEC205+ Dendritic Cell–Targeted Tolerogenic Vaccination Promotes Immune Tolerance in Experimental Autoimmune Arthritis

“…Next, we sought to assess the impact of DEC205 + DC targeting on the generation of PG-specific CD4 + T follicular helper (T FH ) cells, which play a crucial role in the development of GCs and Agspecific B cell immunity (44,45). For this, recipient mice were injected with congenically marked CD4 + TCR-PG + T cells prior to recombinant fusion Ab administration and immunization with PG/ DDA.…”