Cytokines in Follicular Helper T Cell Biology in Physiologic and Pathologic Conditions

Abstract

Follicular helper T cells (Tfh) play a crucial role in generating high-affinity antibodies (Abs) and establishing immunological memory. Cytokines, among other functional molecules produced by Tfh, are central to germinal center (GC) reactions. This review focuses on the role of cytokines, including IL-21 and IL-4, in regulating B cell responses within the GC, such as differentiation, affinity maturation, and plasma cell development. Additionally, this review explores the impact of other cytokines like CXCL13, IL-10, IL-9, and IL-2 on GC responses and their potential involvement in autoimmune diseases, allergies, and cancer. This review highlights contributions of Tfh-derived cytokines to both protective immunity and immunopathology across a spectrum of diseases. A deeper understanding of Tfh cytokine biology holds promise for insights into biomedical conditions.

Keywords: B cell; Cytokine; Follicular helper T cell; Germinal center; Plasma cell.

Figure 1. Influences of cytokines from Tfh on germinal center B cell dynamics. (A) Tfh cells release IL-21, which stimulates both the proliferation and the affinity maturation of B cells, culminating in their differentiation into PCs that synthesize Abs. (B) IL-4 promotes the generation of IgG1 or IgE and the differentiation into IgG1- or IgE-secreting PCs. (C) CXCL13 directs the migration of B cells in humans, IL-9 influences the expansion of certain B cell subsets, and IL-2 enhances the expansion of non-Tfh, Treg, and Tfr cells. See text for comprehensive details. Illustration produced with BioRender (https://BioRender.com/).

Figure 2. Impact of cytokines from Tfh cells in pathological conditions. See text for comprehensive details. Illustration produced with BioRender (https://BioRender.com/).