Follicular T-helper cell recruitment governed by bystander B cells and ICOS-driven motility - PubMed (original) (raw)

. 2013 Apr 25;496(7446):523-7.

doi: 10.1038/nature12058.

Xuanying Li, Dan Liu, Jianfu Li, Xu Zhang, Xin Chen, Shiyue Hou, Lixia Peng, Chenguang Xu, Wanli Liu, Lianfeng Zhang, Hai Qi

Affiliations

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

Heping Xu et al. Nature. 2013.

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.

PubMed Disclaimer

Comment in

Similar articles

Cited by

References

    1. Immunity. 1999 Oct;11(4):423-32 - PubMed
    1. Annu Rev Immunol. 2011;29:621-63 - PubMed
    1. Immunity. 2011 Nov 23;35(5):671-80 - PubMed
    1. Annu Rev Immunol. 2012;30:429-57 - PubMed
    1. Science. 2006 Jun 16;312(5780):1672-6 - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources