Follicular T-helper cell recruitment governed by bystander B cells and ICOS-driven motility.

TitleFollicular T-helper cell recruitment governed by bystander B cells and ICOS-driven motility.
Publication TypeJournal Article
Year of Publication2013
AuthorsXu H, Li X, Liu D, Li J, Zhang X, Chen X, Hou S, Peng L, Xu C, Liu W, Zhang L, Qi H
JournalNature
Volume496
Issue7446
Pagination523-7
Date Published2013 Apr 25
Abstract

Germinal centres support antibody affinity maturation and memory formation. Follicular T-helper cells promote proliferation and differentiation of antigen-specific B cells inside the follicle. A genetic deficiency in the inducible co-stimulator (ICOS), a classic CD28 family co-stimulatory molecule highly expressed by follicular T-helper cells, causes profound germinal centre defects, leading to the view that ICOS specifically co-stimulates the follicular T-helper cell differentiation program. Here we show that ICOS directly controls follicular recruitment of activated T-helper cells in mice. This effect is independent from ICOS ligand (ICOSL)-mediated co-stimulation provided by antigen-presenting dendritic cells or cognate B cells, and does not rely on Bcl6-mediated programming as an intermediate step. Instead, it requires ICOSL expression by follicular bystander B cells, which do not present cognate antigen to T-helper cells but collectively form an ICOS-engaging field. Dynamic imaging reveals ICOS engagement drives coordinated pseudopod formation and promotes persistent T-cell migration at the border between the T-cell zone and the B-cell follicle in vivo. When follicular bystander B cells cannot express ICOSL, otherwise competent T-helper cells fail to develop into follicular T-helper cells normally, and fail to promote optimal germinal centre responses. These results demonstrate a co-stimulation-independent function of ICOS, uncover a key role for bystander B cells in promoting the development of follicular T-helper cells, and reveal unsuspected sophistication in dynamic T-cell positioning in vivo.

DOI10.1371/journal.pntd.0002285
Alternate JournalNature