RNA-sequencing of bulk CD19+ Thymic B cells from young (3 month - 4 year) and old (42 - 61 years) humans

Thymic B cells have been recently shown the ability to be licensed to express Aire, a critical transcription factor involved in the expression of self-antigens in the thymus which are critical for clonal deletion of autoreactive T cells and maintenance of self-tolerance. Mutations in AIRE cause systemic autoimmunity in humans and autoimmunity with varying degrees of severity in different mouse strains. Thymic B cells have been studied in young animals, but studies of this population with age are lacking. Given the thymus undergoes age-associated atrophy in its stromal compartment, we hypothesized that aged thymic B cells may under go changes with age which may impact their ability to mediate clonal deletion of autoreactive T cells and may contribute to age-associated increases in autoimmune prevalence. By comparing the transcriptome of young and aged thymic B cells we find that Aire and transcriptional activators of Aire are signficantly decreased with age.

近期研究证实，胸腺B细胞（Thymic B cells）可获得功能许可以表达自身免疫调节因子（Autoimmune Regulator, AIRE）。该因子是胸腺内自身抗原表达的关键转录因子，而胸腺自身抗原的表达对于自身反应性T细胞的克隆清除及自身耐受的维持至关重要。AIRE基因突变可引发人类全身性自身免疫病，在不同小鼠品系中则会导致程度各异的自身免疫病症。目前针对年轻动物的胸腺B细胞已有较多研究，但关于该细胞群体随年龄变化的相关研究仍较为匮乏。鉴于胸腺的基质区室会发生年龄相关性萎缩，我们提出假说：衰老的胸腺B细胞可能随年龄发生改变，这一改变会影响其介导自身反应性T细胞克隆清除的能力，并可能促使自身免疫病患病率随年龄增长而升高。通过对比年轻与衰老胸腺B细胞的转录组（transcriptome），我们发现AIRE及其转录激活因子的表达水平随年龄增长显著下调。