Abstract
T follicular helper (Tfh) cells are crucial for the establishment of germinal centers (GCs) and potent antibody responses. Nevertheless, the Tcell-intrinsic factors that are required for the maintenance of already-established Tfh cells and GCs remain largely unknown. Here, we use temporally guided gene ablation in CD4+ Tcells to dissect the contributions of the Tfh-associated chemokine receptor CXCR5 and the transcription factor Bcl6. Induced ablation of Cxcr5 has minor effects on the function of established Tfh cells, and Cxcr5-ablated cells still exhibit most of the features of CXCR5+ Tfh cells. In contrast, continued Bcl6 expression is critical to maintain the GC Tfh cell phenotype and also the GC reaction. Importantly, Bcl6 ablation during acute viral infection results in the transdifferentiation of established Tfh into Th1 cells, thus highlighting the plasticity of Tfh cells. These findings have implications for strategies that boost or restrain Tfh cells and GCs in health and disease.
Highlights
T follicular helper (Tfh) cells are critically important for providing help to B cells for potent antibody responses (Crotty, 2019; Vinuesa et al, 2016)
T follicular helper (Tfh) cells are crucial for the establishment of germinal centers (GCs) and potent antibody responses
We use temporally guided gene ablation in CD4+ T cells to dissect the contributions of the Tfh-associated chemokine receptor CXCR5 and the transcription factor Bcl6
Summary
T follicular helper (Tfh) cells are critically important for providing help to B cells for potent antibody responses (Crotty, 2019; Vinuesa et al, 2016). Tfh cells are characterized by the expression of the chemokine receptor CXCR5 and the transcriptional repressor Bcl. Tfh cells are characterized by the expression of the chemokine receptor CXCR5 and the transcriptional repressor Bcl6 They express several co-stimulatory molecules such as inducible T cell co-stimulator (ICOS), CD40L, and B- and T-lymphocyte attenuator (BTLA) and inhibitory receptors such as programmed cell death protein-1 (PD-1) that allow for close interactions with B cells. Tfh cell differentiation is characterized by a multistep differentiation process that involves sequential interactions with dendritic cells (DCs) and B cells in distinct micro-anatomical locations, leading to the establishment of germinal centers (GCs), in which potent antibodies are generated (Crotty, 2019; Qi, 2016; Vinuesa et al, 2016). Localized within GCs, mature GC Tfh cells express the highest levels of CXCR5 and Bcl among CD4+ T cells
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
