期刊
NATURE
卷 496, 期 7446, 页码 523-+出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nature12058
关键词
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资金
- National Natural Science Foundation of China [81072464, 81161120405]
- Program for New Century Excellent Talents in University [20091042000]
- Tsinghua-Yu-Yuan Medical Sciences Fund [20240000585]
- Tsinghua University Initiative Scientific Research Program [2010Z02150]
- Institut Merieux
- Tsinghua-Peking Center for Life Sciences
Germinal centres support antibody affinity maturation and memory formation(1). Follicular T-helper cells promote proliferation and differentiation of antigen-specific B cells inside the follicle(2,3). 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(4,5), leading to the view that ICOS specifically co-stimulates the follicular T-helper cell differentiation program(2,6,7). 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.
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