关键词： 自身免疫性疾病   调节性B细胞   IL-10  

摘要： 调节性B细胞的免疫应答是通过对炎性反应和免疫应答的调节作用,这种B细胞被称之为调节性B细胞。调节性B细胞的调节作用是通过分泌TGF-B和IL-10等调节性细胞因子来影响免疫细胞的功能。所以,知道调节性B细胞的活化机制、在自身免疫性疾病中的作用和生物学功能具有非常重要的意义。

关键词： MULTIPLE-SCLEROSIS   PERIPHERAL-BLOOD   INFECTIOUS TOLERANCE   EFFECTOR FUNCTION   GENE-EXPRESSION   SOLUBLE 4-1BB   IN-VIVO   SUPPRESSION   CD25(+)   FOXP3  

摘要： CD137 is a T cell costimulatory molecule encoded by the prime candidate gene (designated Tnfrsf9) in NOD.B10 Idd9.3 congenic mice protected from type 1 diabetes (T1D). NOD T cells show decreased CD137-mediated T cell signaling compared with NOD. B10 Idd9.3 T cells, but it has been unclear how this decreased CD137 T cell signaling could mediate susceptibility to T1D. We and others have shown that a subset of regulatory T cells (Tregs) constitutively expresses CD137 (whereas effector T cells do not, and only express CD137 briefly after activation). In this study, we show that the B10 Idd9.3 region intrinsically contributes to accumulation of CD137(+) Tregs with age. NOD.B10 Idd9.3 mice showed significantly increased percentages and numbers of CD137(+) peripheral Tregs compared with NOD mice. Moreover, Tregs expressing the B10 Idd9.3 region preferentially accumulated in mixed bone marrow chimeric mice reconstituted with allotypically marked NOD and NOD.B10 Idd9.3 bone marrow. We demonstrate a possible significance of increased numbers of CD137(+) Tregs by showing functional superiority of FACS-purified CD137(+) Tregs in vitro compared with CD137(-) Tregs in T cell-suppression assays. Increased functional suppression was also associated with increased production of the alternatively spliced CD137 isoform, soluble CD137, which has been shown to suppress T cell proliferation. We show for the first time, to our knowledge, that CD137(+) Tregs are the primary cellular source of soluble CD137. NOD.B10 Idd9.3 mice showed significantly increased serum soluble CD137 compared with NOD mice with age, consistent with their increased numbers of CD137(+) Tregs with age. These studies demonstrate the importance of CD137(+) Tregs in T1D and offer a new hypothesis for how the NOD Idd9.3 region could act to increase T1D susceptibility. The Journal of Immunology, 2012, 189: 5001-5015.

关键词： 天疱疮   B淋巴细胞   抗体  

摘要： 目的探讨调节性B细胞（Breg）在天疱疮发病中的免疫介导机制。方法以CD19^＋CD24^hiCD38^hi作为Breg标记，流式细胞仪检测48例天疱疮患者及20例健康人外周血中Breg占CD19^＋B细胞的比例，观察不同严重程度患者的Breg比例变化趋势。采用ELISA法检测患者血清中特异性抗Dsg1、Dsg3抗体滴度、亚型，分析其与Breg比例的相关性。结果天疱疮患者外周血Breg占CDf19＋B细胞的比例（11．54％±0．97％）与健康对照组（8．19％±0．85％）相比差异有统计学意义（P=0．04），且急性期轻度患者该比例（5．17％±2．14％）与中度患者（11．38％±5．30％，P=0．042）、重度患者（11．17％±5．31％，P=0．046）相比，差异均有统计学意义；Breg比例与抗Dsgl抗体亚型IgG4以及IgG4／IgG1的比值均呈正相关（r值分别为0．527，0．565，P值均〈0．01）。结论Breg主要和抗体产生以及疾病活动相关，但其具体的作用机制尚待研究。

关键词： AUTOREACTIVE T-CELLS   CHRONIC ITP   AUTOIMMUNE THROMBOCYTOPENIA   INCREASED FREQUENCY   DEPLETING THERAPY   PURPURA   ROMIPLOSTIM   RITUXIMAB   ELTROMBOPAG   SPLENECTOMY  

摘要： B lymphocytes producing antiplatelet autoantibodies play a major role in autoimmune thrombocytopenia (ITP). However, certain B cells, including the human CD19(+)CD24(hi)CD38(hi) subpopulation, possess regulatory functions mediated partly by IL-10. In a cohort of chronic ITP patients with low platelet counts who consisted of patients off treatment, we found a lower frequency of CD19(+)CD24(hi)CD38(hi) in the peripheral compartment of nonsplenectomized patients (P = .03). IL-10 expression after activation was decreased in all ITP circulating CD19(+) subpopulations (P < .03), and inhibition of monocyte TNF-alpha expression by activated B cells was reduced in patients with platelet numbers of < 50 x 10(9) cells/L (P = .001), indicating that regulatory B cells of patients with ITP are functionally impaired in their ability to dampen monocyte activation. Interestingly, in nonsplenectomized patients whose platelet counts were elevated after treatment with thrombopoietic agents, the frequency of CD19(+)CD24(hi)CD38(hi) B cells was increased compared with those before treatment (P = .02). Altogether, these data indicate a compromised regulatory B-cell compartment as an additional defect in immune regulation in patients with chronic ITP that may be restored in responders to thrombopoietic treatment. (Blood. 2012;120(16):3318-3325)

关键词： 调节性B细胞   IL-10   转化生长因子β   自身免疫性疾病  

摘要： 以往认为，B细胞通过产生特异性抗体提呈抗原产生共刺激分子活化T细胞、并通过细胞因子发挥免疫作用。但是近年来研究发现，B细胞对免疫应答和炎性反应有调节作用，这种B细胞被命名为调节性B细胞（Br）。Br通过分泌调节性的细胞因子IL-10和TGF—β影响B细胞和致病性T细胞之间的相互作用而抑制病理性免疫反应。因而了解Br的生物学功能、活化机制以及在自身免疫性疾病中的作用具有重要意义。

关键词： B细胞   调节性   接触性过敏性皮炎   转化生长因子β1   IL-10   抗原特异性抗体   类风湿性关节炎   调节免疫反应  

摘要： B细胞主要通过产生抗原特异性抗体、辅助诱导CD4＋T细胞活化发挥正向免疫调节作用[1].然而近年动物试验研究表明B细胞可以负向调节免疫反应[2,3],这类B细胞被称为调节性B细胞,并发现缺乏调节性B细胞会导致自身免疫性脑脊髓膜炎、慢性结肠炎、接触性过敏性皮炎、类风湿性关节炎、非肥胖型小鼠糖尿病等疾病的症状恶化.调节性B细胞主要通过产生白细胞介素10（IL-10）或转化生长因子β1（TGF-β1）等细胞因子调节免疫系统.其中产生IL-10的B细胞被称为B10细胞,而占成年小鼠脾脏B细胞1%-3%的CD19hiCD1dhiCD5＋B细胞产生的IL-10占B细胞产生IL-10的大部分[4].

关键词： 高迁移率族蛋白质类   T淋巴细胞,调节性   免疫  

摘要： 目的观察高迁移率族蛋白B1（high mobility group box-1 protein，HMGBl）对分泌IL-10树突状细胞（dendritic cell，DC）亚群CD11c^low CD45RB^high DC功能的影响。方法采用磁珠分选技术获得Bab／c小鼠脾脏CD11c^low CD45RB^high DC和CD4＋T淋巴细胞，加不同浓度HMGB1处理（20，100，500ng／ml，以不加HMGBI的细胞作为对照）CD11c^low CD45RB^high DC细胞；流式细胞术检测CD11c^low CD45RB^high DC表面分子CD40、CD80、CD86、I—a／e及Toll样受体（TLR）4的表达强度；应用ELISA检测CD11c^low CD45RB^high DC培养液中IL-10的含量。将CD4＋T淋巴细胞分为正常对照组（未作任何处理）、未刺激组（加入未经HMGB1处理的CD11c^low CD45RB^high DC与CD4＋T淋巴细胞混合培养）、高浓度HMGB1刺激组（加入经500ng／ml HMGB1处理后的CD11c^low CD45RB^high DC与CD4＋T淋巴细胞混合培养）、高浓度HMGB1刺激＋抗体1组（加入经500ng／ml HMGB1处理后的CD11c^low CD45RB^high DC、抗IL-10抗体与CD4＋T淋巴细胞混合培养）和高浓度HMGBI刺激＋抗体2组（加入经500ng／ml HMGB1处理后的CD11c^low CD45RB^high DC、IL-10的同型对照抗体与CD4＋T淋巴细胞混合培养）。流式细胞术检测CD4＋T淋巴细胞培养液中IL-4和干扰素-γ（IFN-γ）的含量。结果与未加HMGB1刺激相比，HMGB1能显著增强CD11c^low CD45RB^high DC表面分子CD86、TLR4的表达及IL-10的分泌，其中IL-10分泌呈HMGB1浓度依赖性。高浓度HMGB1刺激组IFN-γ水平为（279±17）pg／ml，显著低于未刺激组（963±11）pg／ml（P〈0．05）；高浓度HMGBl刺激组IL-4水平为（3724-14）pg／ml，明显高于未刺激组（213±10）pg／ml（P〈0．05）。结论HMGB1可促进CD11c^low CD45RB^high DC IL-10的分泌，诱导CD4＋T淋巴细胞向Th2型反应分化，通过激活CD11c^low CD45RB^high DC介导机体免疫抑制活性。

关键词： 变应性鼻炎   调节性B细胞   IL-10   CD19  

摘要： 变应性鼻炎是耳鼻喉科的常见疾病之一,是发生在鼻黏膜的变态反应性疾病,发病机制尚未完全清楚。新近有研究表明:一种新的B细胞亚群-调节性B细胞,通过刺激其表面、诱导释放调节性细胞因子如IL-10及CD19等发挥调节作用,可能在变应性鼻炎的发生发展的复杂的免疫调节网络中起着重要的调节作用。

关键词： 调节性B细胞   自身免疫性糖尿病   白细胞介素-10   转化生长因子-β1  

摘要： 调节性B细胞在自身免疫性糖尿病的发生、发展、转归过程中起重要调节作用。通过产生白细胞介素-10（IL-10）和转化生长因子-β1（TGF-β1）等抑制性细胞因子介导免疫耐受。体外诱导分泌TGF-β1的调节性B细胞可以为自身免疫性糖尿病的治疗提供新的方法。抗CD20单克隆抗体治疗自身免疫性糖尿病可使调节性B细胞数量增加。

关键词： FC-GAMMA-RIIB   T-CELLS   INDOLEAMINE 2,3-DIOXYGENASE   IMMUNE-COMPLEXES   INTERFERON-BETA   B10 CELLS   TOLERANCE   MICE   AUTOIMMUNITY   ACTIVATION  

摘要： Regulatory dendritic cells (DCs) play important roles in the induction of peripheral tolerance and control of adaptive immune response. Our previous studies demonstrate that splenic stroma can drive mature DCs to proliferate and further differentiate into a unique subset of CD11b(hi)Ia(low) regulatory DCs, which could inhibit T-cell response, program generation of immunosuppressive memory CD4 T cells. However, the effect of regulatory DCs on B-cell function remains unclear. Here, we report that regulatory DCs can induce splenic B cells to differentiate into a distinct subtype of IL-10-producing regulatory B cells with unique phenotype CD19(hi)Fc gamma IIb(hi). CD19(hi)Fc gamma IIb(hi) B cells inhibit CD4 T-cell response via IL-10. CD19(hi)Fc gamma IIb(hi) B cells have enhanced phagocytic capacity compared with conventional CD19(+) B cells, and Fc gamma RIIb mediates the uptake of immune complex by CD19(hi)Fc gamma IIb(hi) B cells. We found that regulatory DC-derived IFN-beta and CD40 ligand are responsible for the differentiation of CD19(hi)Fc gamma IIb(hi) B cells. Furthermore, an in vivo counterpart of CD19(hi)Fc gamma IIb(hi) B cells in the spleen and lymph nodes with similar phenotype and regulatory function has been identified. Our results demonstrate a new manner for regulatory DCs to down-regulate immune response by, at least partially, programming B cells into regulatory B cells. (Blood. 2012;120(3):581-591)