Interconnected subsets of memory follicular helper T cells have different effector functions

Assia Asrir,Corine Pérals,Nicolas Fazilleau,Mylène Gador,Meryem Aloulou

doi:10.1038/s41467-017-00843-7

Abstract

Follicular helper T cells regulate high-affinity antibody production. Memory follicular helper T cells can be local in draining lymphoid organs and circulate in the blood, but the underlying mechanisms of this subdivision are unresolved. Here we show that both memory follicular helper T subsets sustain B-cell responses after reactivation. Local cells promote more plasma cell differentiation, whereas circulating cells promote more secondary germinal centers. In parallel, local memory B cells are homogeneous and programmed to become plasma cells, whereas circulating memory B cells are able to rediversify. Local memory follicular helper T cells have higher affinity T-cell receptors, which correlates with expression of peptide MHC-II at the surface of local memory B cells only. Blocking T-cell receptor–peptide MHC-II interactions induces the release of local memory follicular helper T cells in the circulating compartment. Our studies show that memory follicular helper T localization is highly intertwined with memory B cells, a finding that has important implications for vaccine design.

Highlights

Follicular helper T cells regulate high-affinity antibody production
Some memory Tfh cells are found retained in the draining lymphoid organs in the B follicle at proximity of memory B cells
Other memory Tfh cells circulate in non-draining lymphoid organs such as the spleen after sc immunization and localize outside the B follicle

Summary

Introduction

Follicular helper T cells regulate high-affinity antibody production. Memory follicular helper T cells can be local in draining lymphoid organs and circulate in the blood, but the underlying mechanisms of this subdivision are unresolved. Blocking T-cell receptor–peptide MHC-II interactions induces the release of local memory follicular helper T cells in the circulating compartment. Effector Tfh cells develop locally in lymphoid organs draining the site of immunization[1] These cells regulate the outcome of humoral responses through a combination of specific T-cell receptor (TCR) interactions with peptide-MHCII (pMHCII), engagement of co-stimulatory molecules and cytokine delivery[2, 3]. These events result in class-switch recombination and somatic diversification of the B-cell receptor (BCR) in the germinal center (GC) and, the selection of high-affinity B-cell variants into the plasma cell and memory B-cell compartment. After Ag reactivation, memory B cells induce rapid effector functions of memory Tfh cells, establishing the close relationship between memory B cells and memory Tfh cells[36]

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Conclusion