GPR174-CCL21调控体液免疫应答的两性差异

体液免疫应答具有明显的两性差异。通常女性产生的针对外来病原体或者自身抗原的抗体水平相比男性更高,因此女性比男性更容易清除病原体的感染,但女性也比男性更容易患自身免疫疾病。长效且高亲和力的体液免疫应答依赖由B细胞形成的生发中心(germinal center,GC)反应,然而B细胞形成GC的能力是否存在两性差异从而直接导致体液免疫应答的两性差异尚不清楚。该研究提出了一套在分子和细胞水平上解释体液免疫应答两性差异的新机制,即雄激素可以增强B细胞表达的GPR174在接收到CCL21信号后与Gαi蛋白的结合水平,由此促进雄性B细胞更多地迁移在滤泡外周,而不能更多地迁移至滤泡中心形成GC及抗体应答,从而直接介导体液免疫应答的两性差异。该研究为解决在增强保护性疫苗抗体应答水平以及治疗自身免疫疾病时遇到的B细胞介导的两性差异问题提供了新的见解。

A GPR174-CCL21 module imparts sexual dimorphism to humoral immunity

Humoral immune responses have long been known to possess significant sexual dimorphism.For instance,women generally mount higher levels of antibodies than men,rendering them more effective to clear pathogens,while more prone to develop autoimmune diseases.Humoral immune responses are dependent on the B cell-established germinal center(GC)reaction,whereby generating long-lived antibody responses with high affinity.However,it is not clear whether B cells themselves is capable to generate GC in a sexual dimorphic manner which directly leads to sexual dimorphism of humoral immune responses.This study establishes a novel mechanism underlying the sexual dimorphic humoral immune response,in which the male hormones could promote GPR174-Gαi association on B cells to direct migration toward CCL21,allowing the male B cells to return less to the follicle center than the female B cells and reducing the male B cell-generated GC response,thus mediating the sexual dimorphism in humoral immune response.These findings provide new insights into the fine-tuning B-cell mediated sexual dimorphism in vaccine antibody responses and autoimmune disease susceptibility.