Abstract:
The production of antibodies can constitute a powerful protective mechanism against infection, but antibodies can also participate in autoimmunity and allergic responses. Recent advances in the understanding of the regulation of germinal centres (GC), the sites where B cells acquire the ability to produce high-affinity antibodies, offered new prospects for the modulation of antibody production in autoimmunity and vaccination. The process of B cell affinity maturation and isotype switching requires signals from T follicular helper (Tfh) cells. In addition, Foxp3+ T follicular regulatory (Tfr) cells represent the regulatory counterpart of Tfh in the GC reaction. Tfr cells were identified one decade ago and since then it has become clear their role in controlling the emergence of autoreactive B cell clones following infection and immunization. At the same time, Tfr cells are essential for fine-tuning important features of the humoral response directed to foreign antigens that are critical in vaccination. However, this regulation is complex and several aspects of Tfr cell biology are yet to be disclosed. Here, we review the current knowledge about the regulation of antibody responses against self and foreign antigens by Tfr cells and its implications for the future rational design of safer and more effective vaccines.
摘要:
抗体的产生可以构成强大的抗感染保护机制,但是抗体也可以参与自身免疫和过敏反应。对生发中心(GC)调节的理解的最新进展,B细胞获得产生高亲和力抗体能力的部位,为自身免疫和疫苗接种中抗体产生的调节提供了新的前景。B细胞亲和力成熟和同种型转换的过程需要来自T滤泡辅助(Tfh)细胞的信号。此外,Foxp3+T卵泡调节(Tfr)细胞代表GC反应中Tfh的调节对应物。Tfr细胞是在十年前鉴定的,从那时起,它们在控制感染和免疫后自身反应性B细胞克隆出现中的作用就变得很清楚了。同时,Tfr细胞对于微调针对在疫苗接种中至关重要的外来抗原的体液应答的重要特征是必不可少的。然而,这种调节是复杂的,Tfr细胞生物学的几个方面尚未公开。这里,我们回顾了目前有关Tfr细胞调节针对自身抗原和外来抗原的抗体应答的知识,及其对未来合理设计更安全、更有效的疫苗的意义.