Follicular helper T‐cell memory: establishing new frontiers during antibody response

Abstract

The generation of immunological memory during an immune response is a hallmark of the adaptive immune system. Follicular helper T (Tfh) cells are a CD4 þ T-cell subset specialised to regulate antibody response. Emerging evidence suggests that during antibody response, Tfh memory is generated along with the generation of B-cell memory. There are multiple layers for the differentiation and function of memory Tfh cells. Both early committed precursor Tfh cells and effector Tfh cells exiting germinal centres can contribute to the memory Tfh pool. Functionally, memory Tfh cells not only enhance a secondary response upon antigen rechallenge but also circulate to non-draining lymph tissues to differentiate into effector Tfh cells in the face of systemic antigen/pathogen spreading, thus also promoting a primary response. Circulating memory Tfh cells are a valuable marker to monitor the Tfh programme in human autoimmune diseases, infections and vaccinations. Future studies are required to understand the molecular mechanisms determining the commitment and plasticity of Tfh memory and hence the physiological functions of Tfh memory. Keywords: Tfh; memory; antibody; plasticity Host detection of invading pathogens triggers a cascade of events that culminate in the recruitment and differentiation of leukocytes, including lymphocytes, suited to eliminate the pathogen. The generation of memory from efficacious immune response provides long-term protection against the pathogen. For humoral immune memory, long-lived plasma cells sustain antibody levels, whereas memory B cells respond rapidly upon antigen rechallenge. 1 As a result, omnipresent high-affinity serum antibodies prevent pathogens from entering or damaging host cells, mediate opsonisation, increase the efficiency of antigen presentation through the formation of immune complexes and stimulate immune responses via Fc (Fragment, crystallisable) or complement receptors.Cognate helper from CD4 þ helper T cells is essential at each step to generate B-cell memory: B-cell priming, germinal centre (GC) formation, selection and development of long-lived plasma cells and memory B cells, and memory B-cell response upon antigen rechallenge. 2 Although the generation and function of B-cell memory have been studied extensively (see ), the generation and function of cognate helper T-cell memory has not enjoyed as much limelight. Follicular B helper T (Tfh) cells are a CD4 þ helper T-cell subset specialised to provide cognate help to B cells. [3][4][5][6][7] In this review, we will focus on recent evidence for the formation of Tfh memory. As many important questions remain unanswered, the discussion here hopefully will inspire further investigation. THE NEED FOR TFH MEMORY-LEARNING FROM B-CELL MEMORYIn a recall antibody response, memory B cells undergo accelerated clonal expansion and rapid differentiation to high-affinity plasma cells or GC B cells. There are contradictory results on whether cognate T-cell help is required for memory B cells to respond in a recall response. CD4 þ hel...

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