Department of Brain Sciences, Imperial College London, London, UK.
Department of Brain Sciences, Imperial College London, London, UK/Imperial College Healthcare NHS Trust, London, UK.
Mult Scler. 2021 Jul;27(8):1187-1197. doi: 10.1177/1352458520951536. Epub 2020 Sep 14.
Multiple sclerosis (MS) is characterized by central nervous system (CNS) infiltration of T and B cells, excess inflammatory cytokine and chemokine production and failure of immune regulation. CD19+CD24CD38 transitional B cells producing interleukin (IL)-10 have been shown to suppress interferon-γ (IFNγ) and tumour necrosis factor-α (TNFα) production by CD4+ T cells and to be dysfunctional in autoimmune arthritis and systemic lupus erythematosus.
We hypothesized that transitional B-cell-dependent immune regulation could be defective in MS and examined their function in healthy subjects and patients with relapsing-remitting multiple sclerosis (RRMS).
A total of 62 healthy donors and 21 RRMS subjects donated peripheral blood for the study. IL-10-producing B cells, IFNγ and TNFα-producing T cells and proliferating T cells were quantified by flow cytometry.
In healthy individuals, CD19+CD24CD38 transitional B cells produce more IL-10 than CD19+CD24+CD38+ naive and CD19+CD24CD38- memory B cells and are able to suppress CD4+ T-cell proliferation and IFNγ and TNFα-production. In subjects with RRMS, CD19+CD24CD38 transitional B cells produce significantly less IL-10 and to fail to suppress effector T-cell function.
CD19+CD24CD38 transitional B cells physiologically represent the most potent regulatory B-cell subset and are functionally defective in patients with RRMS, an abnormality that may contribute to the immune pathological process.
多发性硬化症（MS）的特征是中枢神经系统（CNS）浸润 T 和 B 细胞、过度产生炎症细胞因子和趋化因子以及免疫调节失败。已经表明，产生白细胞介素（IL）-10 的 CD19+CD24CD38 过渡性 B 细胞可抑制 CD4+T 细胞产生干扰素-γ（IFNγ）和肿瘤坏死因子-α（TNFα），并且在自身免疫性关节炎和系统性红斑狼疮中功能失调。
我们假设过渡性 B 细胞依赖性免疫调节可能在 MS 中存在缺陷，并检查其在健康受试者和复发缓解型多发性硬化症（RRMS）患者中的功能。
共有 62 名健康供体和 21 名 RRMS 受试者捐献外周血进行研究。通过流式细胞术定量测定产生 IL-10 的 B 细胞、产生 IFNγ 和 TNFα 的 T 细胞和增殖的 T 细胞。
在健康个体中，CD19+CD24CD38 过渡性 B 细胞比 CD19+CD24+CD38+幼稚 B 细胞和 CD19+CD24CD38-记忆 B 细胞产生更多的 IL-10，并且能够抑制 CD4+T 细胞增殖和 IFNγ 和 TNFα 的产生。在 RRMS 受试者中，CD19+CD24CD38 过渡性 B 细胞产生的 IL-10 明显减少，并且无法抑制效应 T 细胞的功能。
CD19+CD24CD38 过渡性 B 细胞在生理上代表最有效的调节性 B 细胞亚群，并且在 RRMS 患者中功能失调，这种异常可能导致免疫病理过程。
