Characterization of Regulatory B Cells in Graves' Disease and Hashimoto's Thyroiditis.

Characterization of Regulatory B Cells in Graves' Disease and Hashimoto's Thyroiditis.
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DOI:
10.1371/journal.pone.0127949
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发表时间:
2015
期刊:
影响因子:
3.7
通讯作者:
Nielsen CH
Nielsen CH
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Kristensen B;Hegedüs L;Lundy SK;Brimnes MK;Smith TJ;Nielsen CH

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调节性B细胞的一个特征是产生IL-10,因此它们被称为IL-10+ B细胞。对于自身抗原在Graves病(GD)、桥本甲状腺炎(HT)或其他自身免疫性疾病中诱导IL-10+ B细胞的能力知之甚少。我们从12名HT患者、12名GD患者和12名健康供者的甲状腺自身抗原、甲状腺球蛋白(TG)中脉冲纯化B细胞,并将B细胞添加到剩余的外周血单核细胞(PBMCs)中。该方法可诱导GD患者IL-10+ b细胞分化。在健康供体中观察到类似的趋势,但在HT患者的细胞中没有观察到。在GD中,B细胞介导TG诱导产生il -10的CD4+ T细胞。用PMA/ iononomycin刺激PBMCs,以评估三组供体诱导IL-10+ B细胞的最大频率。三组患者IL-10+ b细胞频率相似,且与GD患者游离T3水平相关。来自两组患者的IL-10+ B细胞比来自健康供者的IL-10+ B细胞更频繁地显示CD25或TIM-1。先前与b细胞调节功能相关的两种表面标记组合CD24hiCD38hi和CD27+CD43+的b细胞表达在患者和健康供者之间没有差异。总之,我们的研究结果表明自身免疫性甲状腺炎与IL-10+ B细胞频率降低无关。然而,这些结果并不能排除调节性b细胞功能障碍。我们还讨论了患者和健康供者IL-10+ B细胞的表型差异。
A hallmark of regulatory B cells is IL-10 production, hence their designation as IL-10+ B cells. Little is known about the ability of self-antigens to induce IL-10+ B cells in Graves’ disease (GD), Hashimoto’s thyroiditis (HT), or other autoimmune disease. Here we pulsed purified B cells from 12 HT patients, 12 GD patients, and 12 healthy donors with the thyroid self-antigen, thyroglobulin (TG) and added the B cells back to the remaining peripheral blood mononuclear cells (PBMCs). This procedure induced IL-10+ B-cell differentiation in GD. A similar tendency was observed in healthy donors, but not in cells from patients with HT. In GD, B cells primed with TG induced IL-10-producing CD4+ T cells. To assess the maximal frequency of inducible IL-10+ B cells in the three donor groups PBMCs were stimulated with PMA/ionomycin. The resulting IL-10+ B-cell frequency was similar in the three groups and correlated with free T3 levels in GD patients. IL-10+ B cells from both patient groups displayed CD25 or TIM-1 more frequently than did those from healthy donors. B-cell expression of two surface marker combinations previously associated with regulatory B-cell functions, CD24hiCD38hi and CD27+CD43+, did not differ between patients and healthy donors. In conclusion, our findings indicate that autoimmune thyroiditis is not associated with reduced frequency of IL-10+ B cells. These results do not rule out regulatory B-cell dysfunction, however. The observed phenotypic differences between IL-10+ B cells from patients and healthy donors are discussed.
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