CD4+ T cells that help B cells - a proposal for uniform nomenclature

Abstract

T follicular helper (Tfh) cells cognately guide differentiation of antigen-primed B cells in secondary lymphoid tissues. 'Tfh-like' populations not expressing the canonical Tfh cell transcription factor BCL6 have also been described, which can aid particular aspects of B cell differentiation. Tfh and Tfh-like cells are essential for protective and pathological humoral immunity. These CD4⁺ T cells that help B cells are polarized to produce diverse combinations of cytokines and chemokine receptors and can be grouped into distinct subsets that promote antibodies of different isotype, affinity, and duration, according to the nature of immune challenge. However, unified nomenclature to describe the distinct functional Tfh and Tfh-like cells does not exist. While explicitly acknowledging cellular plasticity, we propose categorizing these cell states into three groups based on phenotype and function, paired with their anatomical site of action.

Figure 1:. Nomenclature used for CD4⁺ T cells that help B cells in different anatomic locations in mice and humans.

Left, Tfh and Tfh-like subsets are shown in regions of secondary lymphoid organs (SLOs) with particular functions depicted. Shown is a region of a lymph node, although similar structures exist in other SLOs. Extrafollicular T follicular helper (EFTfh); T follicular regulatory (Tfr); Natural killer Tfh (NKTfh); Secondary lymphoid organ Tfh (SLO Tfh); Plasmablast (PB); Antibody secreting cell (ASC); Germinal center B cell (GCB); Memory B (mB). Right, Tfh and related subsets in tissues and the blood with general anatomic distinctions and select functions indicated. Circulating Tfh (cTfh); T peripheral helper (Tph); T resident helper (Trh).

Key Figure, Figure 2:. Proposed unified groups of Tfh and Tfh-like cells.

The schema depicts the proposed members of each group with one representative “functional” Tfh cell shown expressing the classic Tfh-defining chemokine receptor CXCR5. Signature cytokines along with the canonical cytokine IL-21 are shown but represent the group members without indicating a static state. For example, IL-21 may be produced during particular time windows rather than continuously and other cytokines such as IL-4 may be expressed by cells of all groups but at lower amounts than group 2. Each group encompasses Tfh and Tfh-like cells that can function at different sites within SLOs as well as outside of SLOs, with the central theme of the group being the similar transcription factor and cytokine expression patterns. Cooperation of the group members ultimately results in the production of the types of antibodies depicted at the bottom of the image, as well as humoral immunity to the types of challenges listed at the top.