For the ILC and DC fields, unified nomenclature has enabled cross-comparison in work performed by different groups [16]. T and B cells against a variety of pathogens, including Cyanidin chloride viruses, bacteria, helminths, and fungi. While cellular immunity is mediated by cytotoxic Cyanidin chloride CD8+ T lymphocytes and effector CD4+ T lymphocytes (T helper cells), antibodies produced by plasmablasts and plasma cells constitute the humoral arm of adaptive immune responses. Together, both arms complement each others role in fighting infections and in generating immunological HA6116 memory, but they may also be dysregulated in patients suffering from cancer, allergy, immunodeficiency, or autoimmunity. Most long-lived highly specific antibody responses require help from CD4+ T cells. Originally, the CD4+ T helper type (Th)2 cell subset was thought to be responsible for directing antibody responses. Work from the past two decades has corrected and refined this model with the identification of T follicular helper (Tfh) cells –a subset of CD4+ T cells responsible for directing antibody production to a wide array of immune stimuli. However, unified nomenclature to describe functional Tfh and Tfh-like cells is currently lacking. Here, we propose a three-group nomenclature system to categorize these helper subsets based on phenotype, function, and anatomical localization. Tfh cell differentiation and functional heterogeneity Tfh cells are the primary T cells responsible for supporting B cell proliferation, survival, and differentiation in humans and mice. Their recognition as a functionally distinct T helper cell subset was facilitated by the identification of the chemokine receptor CXCR5 as a hallmark of B cell helper function, followed by the discovery of B cell lymphoma 6 (BCL6) as the key transcriptional regulator of Tfh cell differentiation [1C3]. Unlike other effector T helper cells, Tfh cells typically act in secondary lymphoid organs (SLOs), where they interact with B cells at multiple sites, including the T-B border inside B cell follicles and in germinal centers (GCs), to direct the isotype, specificity, and affinity of the B cell response through both contact-dependent signals and the production of cytokines (Box 1, Fig.?Fig.1,1, Table 1). Open in a separate window Figure 1: Nomenclature used for CD4+ T cells that help B cells in different anatomic locations in mice and humans.is required for development, even if it is no longer highly Cyanidin chloride expressed. Secondary lymphoid organs (SLO) include lymph nodes, spleen, Peyers Patches, etc. cTfh, circulating Tfh; EF, extrafollicular; GC, germinal center; NKTfh, Natural killer Tfh; Tfh, T follicular helper; Tfr, T follicular regulatory; Th, T helper; Tph, T peripheral helper; Trh, T resident helper; PB, peripheral blood; CSR, class switch recombination. Grey text indicates the cell subsets that have not been well defined. B cell activationTrhYESTrh1Trh2Trh17Reactivation of memory Cyanidin chloride B cells in situ Open in a separate window Box 1.?The nature of B cell help provided by Tfh cells depends on where they are located Tfh cells are named for their ability to provide help to the recirculating mature B cell pool, also known as follicular B cells, due to Cyanidin chloride their migration between follicles of secondary lymphoid organs (SLO) (Fig. 1). Tfh cells can encounter recirculating follicular B cells at the borders between the T cell zones and the follicles (T-B border), in the B cell follicle, the interfollicular region, and in germinal centers (GC). During responses to protein antigens, the first cognate encounter between primed CXCR5+ CD4+ Tfh cells and B cells that have bound antigen typically occurs at the T-B border [83]. Here, Tfh and/or Tfh-like cells provide co-stimulatory signals, including CD40L and cytokines, to B cells, which initiate their differentiation and direct immunoglobulin (Ig) isotype switching [14, 84]. CD4+ T cells expressing intermediate amounts of CXCR5, immune checkpoint receptor programmed death-1 (PD-1), and BCL6, interacting with B cells at the T:B border have been called pre-GC Tfh cells, pre-Tfh cells, or Tfh cells [85]. We propose referring to them as Tfh cells, to.