在生发中心(GC)反应期间,控制类开关重组和体细胞超突变的基因中的突变可导致多种免疫功能障碍。特别是,CD40LG中的突变,CD40,AICDA,或UNG导致高IgM(HIGM)综合征,一组异质性的原发性免疫缺陷。卵泡辅助性T细胞(Tfh)和卵泡调节性T细胞(Tfr)在GCs的形成和调节中起关键作用,但它们在HIGM发病机制中的作用仍然有限。这里,我们发现,与CD40配体(CD40L)-和活化诱导的胞苷脱氨酶(AICDA)缺陷患者相比,在CD40缺乏的儿童中,循环Tfh和Tfr细胞在频率和激活表型方面受到严重损害。这些发现为人类Tfh生物学提供了有用的见解,这对于理解由CD40突变引起的HIGM综合征的分子基础具有潜在的意义。
Mutations in genes that control class switch recombination and somatic hypermutation during the germinal center (GC) response can cause diverse immune dysfunctions. In particular, mutations in CD40LG, CD40, AICDA, or UNG cause hyper-IgM (HIGM) syndrome, a heterogeneous group of primary immunodeficiencies. Follicular helper (Tfh) and follicular regulatory (Tfr) T cells play a key role in the formation and regulation of GCs, but their role in HIGM pathogenesis is still limited. Here, we found that compared to CD40 ligand (CD40L)- and activation-induced cytidine deaminase (AICDA)-deficient patients, circulating Tfh and Tfr cells were severely compromised in terms of frequency and activation phenotype in a child with CD40 deficiency. These findings offer useful insight for human Tfh biology, with potential implications for understanding the molecular basis of HIGM syndrome caused by mutations in CD40.