A GPR174-CCL21 module imparts sexual dimorphism to humoral immunity

doi:10.1038/s41586-019-1873-0

GSTDTAP > 地球科学

DOI	10.1038/s41586-019-1873-0
	A GPR174-CCL21 module imparts sexual dimorphism to humoral immunity
	Morley, Jessica 1; Cowls, Josh 1; Taddeo, Mariarosaria 1,2; Floridi, Luciano 3,4
	2020-06-01
发表期刊	NATURE
ISSN	0028-0836
EISSN	1476-4687
出版年	2020
卷号	577 期号:7790 页码:416-+
文章类型	Article
语种	英语
国家	Peoples R China; England; USA
英文关键词	Humoral immune responses to immunization and infection and susceptibilities to antibody-mediated autoimmunity are generally lower in males(1-3). However, the mechanisms underlying such sexual dimorphism are not well understood. Here we show that there are intrinsic differences between the B cells that produce germinal centres in male and female mice. We find that antigen-activated male B cells do not position themselves as efficiently as female B cells in the centre of follicles in secondary lymphoid organs, in which germinal centres normally develop. Moreover, GPR174-an X-chromosome-encoded G-protein-coupled receptor-suppresses the formation of germinal centres in male, but not female, mice. This effect is intrinsic to B cells, and correlates with the GPR174-enhanced positioning of B cells towards the T-cell-B-cell border of follicles, and the distraction of male, but not female, B cells from S1PR2-driven follicle-centre localization. Biochemical fractionation of conditioned media that induce B-cell migration in a GPR174-dependent manner identifies CCL21 as a GPR174 ligand. In response to CCL21, GPR174 triggers a calcium flux and preferentially induces the migration of male B cells GPR174 also becomes associated with more G alpha i protein in male than in female B cells. Male B cells from orchidectomized mice exhibit impaired GPR174-mediated migration to CCL21, and testosterone treatment rescues this defect. Female B cells from testosterone-treated mice exhibit male-like GPR174-G alpha i association and GPR174-mediated migration. Deleting GPR174 from male B cells causes more efficient positioning towards the follicular centre, the formation of more germinal centres and an increased susceptibility to B-cell-dependent experimental autoimmune encephalomyelitis. By identifying GPR174 as a receptor for CCL21 and demonstrating its sex-dependent control of B-cell positioning and participation in germinal centres, we have revealed a mechanism by which B-cell physiology is fine-tuned to impart sexual dimorphism to humoral immunity.
领域	地球科学 ; 气候变化 ; 资源环境
收录类别	SCI-E
WOS记录号	WOS:000509570100041
WOS关键词	B-CELL MIGRATION ; LYMPHOID ORGANS ; RECEPTOR
WOS类目	Multidisciplinary Sciences
WOS研究方向	Science & Technology - Other Topics
引用统计
文献类型	期刊论文
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/281131
专题	地球科学资源环境科学气候变化
作者单位	1.Univ Oxford, Oxford Internet Inst, Oxford, England; 2.Alan Turing Inst, London, England; 3.Univ Oxford, Oxford Internet Inst, Philosophy & Eth Informat, Oxford, England; 4.Alan Turing Inst, Eth Grp, London, England
推荐引用方式 GB/T 7714	Morley, Jessica,Cowls, Josh,Taddeo, Mariarosaria,et al. A GPR174-CCL21 module imparts sexual dimorphism to humoral immunity[J]. NATURE,2020,577(7790):416-+.
APA	Morley, Jessica,Cowls, Josh,Taddeo, Mariarosaria,&Floridi, Luciano.(2020).A GPR174-CCL21 module imparts sexual dimorphism to humoral immunity.NATURE,577(7790),416-+.
MLA	Morley, Jessica,et al."A GPR174-CCL21 module imparts sexual dimorphism to humoral immunity".NATURE 577.7790(2020):416-+.