Defective Function of CD24+ CD38+ Regulatory B Cells in Ankylosing Spondylitis
Defective Function of CD24+ CD38+ Regulatory B Cells in Ankylosing Spondylitis
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DOI：
10.1089/dna.2015.3046
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发表时间：
2016-02-01
影响因子：
3.1
通讯作者：
Li, Shufeng
中科院分区：
文献类型：
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作者：
Chen, Meng;Zhang, Lei;Li, Shufeng
强直性脊柱炎（AS）是一种与HLA-B*27密切相关的慢性炎症性风湿性疾病，HLA-B*27是一种向T细胞呈递肽抗原的主要组织相容性复合体（MHC）分子。以前，调节B细胞被发现抑制T细胞介导的自身免疫诱导和慢性炎症，部分通过白细胞介素（IL）-10的生产。在这里，我们研究了调节性B细胞在AS发病机制中的作用。采集HLA-B*27阳性AS患者和非AS健康对照的单采样本。我们发现，尽管AS患者和非AS对照组的CD 24（+）CD 38（+）B细胞的频率相似，但与非AS对照组相比，AS患者在体外条件下以及在CD 40和B细胞受体（BCR）刺激后产生的IL-10较少。纯化的T细胞-B细胞共培养物显示，与非AS对照相比，来自AS患者的CD 24（+）CD 38（+）B细胞在抑制初始和记忆CD 8（+）T细胞活化方面存在缺陷。非AS对照中记忆CD 8（+）T细胞的抑制似乎是由IL-10介导的，因为添加IL-10 mAb抑制了CD 24（+）CD 38（+）B细胞介导的促炎细胞因子产生和增殖的下调。为了挽救AS患者的缺陷，用CD 40和BCR刺激预处理CD 24（+）CD 38（+）B细胞，从而增强CD 24（+）CD 38（+）B B细胞介导的记忆CD 8（+）T细胞抑制。总之，我们的数据发现了AS患者的调节性B细胞缺陷。
Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease strongly associated with HLA-B*27, an major histocompatibility complex (MHC) molecule that presents peptide antigen to T cells. Previously, regulatory B cells were found to suppress T cell-mediated autoimmunity induction and chronic inflammation, partially through interleukin (IL)-10 production. Here, we examined the role of regulatory B cells in AS pathogenesis. Apheresis samples from HLA-B*27-positive AS patients and non-AS healthy controls were collected. We found that although AS patients and non-AS controls presented similar frequencies of CD24(+)CD38(+) B cells, compared to non-AS controls, those from AS patients produced less IL-10 under ex vivo condition and after CD40 and B-cell receptor (BCR) stimulation. Purified T cell-B cell cocultures showed that compared to non-AS controls, CD24(+)CD38(+) B cells from AS patients were defective at suppressing naive and memory CD8(+) T cell activation. The suppression of memory CD8(+) T cells in non-AS controls appeared to be mediated by IL-10, since the addition of IL-10 mAb suppressed CD24(+)CD38(+) B cell-mediated downregulation of proinflammatory cytokine production and proliferation. To rescue the defect in AS patients, CD24(+)CD38(+) B cells were pretreated by CD40 and BCR stimulation, which enhanced CD24(+)CD38(+) B cell-mediated memory CD8(+) T cell suppression. Together, our data discovered a regulatory B cell defect in AS patients.