关键词： 调节性B细胞   IL-10   自身免疫病  

摘要： 传统意义上的B淋巴细胞通过呈递自身抗原、产生自身抗体及分泌细胞因子等多种机制在自身免疫病中发挥重要的作用。但是目前发现,另有一群具有特殊免疫表型的调节性B细胞可发挥负向免疫调节作用,参与诱导免疫耐受。本文综述了近年来国内外对自身免疫病及相应的鼠模型中调节性B细胞的研究进展,展示其在自身免疫病中的作用及其可能机制,为自身免疫病的临床治疗提供理论基础。

关键词： 发病机制   溃疡性结肠炎   辅助性T细胞   B细胞   调节性   免疫反应异常   炎症性肠病   常见疾病  

摘要： 炎症性肠病（inflammatory bowel disease，IBD）患病率在国内外均呈上升趋势，已成为消化系统的常见疾病。IBD的病因和发病机制尚未完全明确，目前认为主要包括环境、遗传、感染和免疫等因素。大量研究表明，肠道黏膜免疫反应异常激活是导致IBD发生、

关键词： ALLERGIC AIRWAY DISEASE   IMMUNE-RESPONSES   CUTTING EDGE   RHEUMATOID-ARTHRITIS   IL-10 PRODUCTION   LUPUS MICE   T-CELLS   ACTIVATION   INFLAMMATION   SUPPRESSION  

摘要： T cell Ig domain and mucin domain protein 1 (TIM-1) is a costimulatory molecule that regulates immune responses by modulating CD4(+) T cell effector differentiation. However, the function of TIM-1 on other immune cell populations is unknown. Here, we show that in vivo in mice, TIM-1 is predominantly expressed on B rather than T cells. Importantly, TIM-1 was expressed by a large majority of IL-10-expressing regulatory B cells in all major B cell subpopulations, including transitional, marginal zone, and follicular B cells, as well as the B cell population characterized as CD1d(hi)CD5(+). A low-affinity TIM-1-specific antibody that normally promotes tolerance in mice, actually accelerated (T cell-mediated) immune responsiveness in the absence of B cells. TIM-1(+) B cells were highly enriched for IL-4 and IL-10 expression, promoted Th2 responses, and could directly transfer allograft tolerance. Both cytokine expression and number of TIM-1(+) regulatory B cells (Bregs) were induced by TIM-1-specific antibody, and this was dependent on IL-4 signaling. Thus, TIM-1 is an inclusive marker for IL-10(+) Bregs that can be induced by TIM-1 ligation. These findings suggest that TIM-1 may be a novel therapeutic target for modulating the immune response and provide insight into the signals involved in the generation and induction of Bregs.

关键词： B细胞   自身免疫疾病   慢性炎症疾病   调节性   分泌抗体   免疫调节因子   免疫调节作用   白细胞介素  

摘要： B细胞具有分泌抗体、抗原提呈、分泌免疫调节因子等作用,在免疫应答中主要产生正向调节作用。近期研究发现,自身免疫病小鼠部分B细胞通过分泌白细胞介素10（IL-10）等细胞因子,发挥负向免疫调节作用。这部分B细胞已被命名为调节性B细胞,

关键词： E3 UBIQUITIN LIGASE   DENDRITIC CELLS   IN-VIVO   CUTTING EDGE   IMMUNOLOGICAL-TOLERANCE   THYMIC SELECTION   PRESENTING CELL   CBL-B   MICE   EXPANSION  

摘要： Multiple mechanisms operate to ensure T-cell tolerance toward self-antigens. Three main processes have been described: clonal deletion, anergy, and deviation to CD4(+) regulatory T cells (Tregs) that suppress autoreactive T cells that have escaped the first 2 mechanisms. Although it is accepted that dendritic cells (DCs) and B cells contribute in maintaining T-cell tolerance to self-antigens, their relative contribution and the processes involved under physiologic conditions remain only partially characterized. In this study, we used different transgenic mouse models to obtain chimeras where a neo self-antigen is expressed by thymic epithelium and/or by DCs or B cells. We found that expression of cognate ligand in the thymus enhances antigen-specific FoxP3(+) cells independently of whether the self-antigen is expressed on thymic epithelium or only on DCs, but not on B cells. On the contrary, self-antigen expression by B cells was very efficient in inducing FoxP3(+) cells in the periphery, whereas self-antigen expression by DC led mainly to deletion and anergy of antigen-specific FoxP3(+) cells. The results presented in this study underline the role of B cells in Treg induction and may have important implications in clinical protocols aimed at the peripheral expansion of Tregs in patients. (Blood. 2011;118(4):984-991)

关键词： B10   IL-10   Breg  

摘要： 白细胞介素10(IL-10)是一种高效的抗炎因子,IL-10通过阻断促炎因子、趋化因子等的作用,发挥其抗炎症作用。最近研究表明,B细胞中存在对免疫应答具有调控作用的调节性B细胞(Bregs),而能产生IL-10的调节性B细胞(B10细胞)在炎症、自身免疫病等疾病的治疗中都有重要的免疫调节作用。

关键词： 调节性B细胞   白细胞介素10   炎性反应   免疫耐受  

摘要： B细胞主要通过呈递抗原和产生抗体在自身免疫病的发生、发展中发挥重要作用。近来研究发现,B细胞对免疫应答和炎性反应有免疫调节作用,这部分B细胞被命名为调节性B细胞(Bregs)。Bregs可通过产生白细胞介素10或转化生长因子β1等抑制性细胞因子介导免疫耐受,抑制过度炎性反应。Bregs在一些自身免疫病小鼠模型(包括实验室性自身免疫脑脊髓炎、炎性肠病、1型糖尿病、系统性红斑狼疮、胶原诱发性关节炎)的发生、发展中起重要的调节作用。Bregs的发现和作用机制的阐明将为全面深入了解自身免疫病免疫耐受的机制及寻求治疗方法提供理论依据。本文综述Bregs的生物学功能、来源与活化及其参与一些器官特异性和非器官特异性自身免疫病的调节作用,并探讨Bregs在人体中存在的可能性。

关键词： CUTTING EDGE   GRANZYME-B   IN-VITRO   WASP   HOMEOSTASIS   ACTIVATION   LYMPHOCYTES  

摘要： Wiskott-Aldrich syndrome (WAS) is an inherited immunodeficiency characterized by high incidence of autoantibody-mediated autoimmune complications. Such a feature has been associated with defective suppressor activity of WAS protein-deficient, naturally occurring CD4(+)CD25(+)Foxp3(+) regulatory T cells on responder T cells. However, it remains to be established whether the altered B-cell tolerance reported in WAS patients and Was knockout (WKO) mice is secondary to abnormalities in the direct suppression of B-cell function by nTreg cells or to impaired regulation of T-helper function. Because activated nTreg cells are known to induce granzyme B-mediated B-cell killing, we decided to evaluate the regulatory capabilities of WKO nTregs on B lymphocytes. We found that preactivated WKO nTreg cells failed to effectively suppress B-cell proliferation and that such a defect was associated with reduced killing of B cells and significantly decreased degranulation of granzyme B. Altogether, these results provide additional mechanistic insights into the loss of immune tolerance in WAS. (Blood. 2011;117(24):6608-6611)

关键词： EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS   T-CELLS   ISCHEMIC-STROKE   BRAIN ISCHEMIA   RAT-BRAIN   MICE   LYMPHOCYTES   INTERLEUKIN-10   IL-10   NEUROPROTECTION  

摘要： Evaluation of infarct volumes and infiltrating immune cell populations in mice after middle cerebral artery occlusion (MCAO) strongly implicates a mixture of both pathogenic and regulatory immune cell subsets in stroke pathogenesis and recovery. Our goal was to evaluate the contribution of B cells to the development of MCAO by comparing infarct volumes and functional outcomes in wild-type (WT) versus B-cell-deficient mu MT(-/-) mice. The results clearly demonstrate larger infarct volumes, higher mortality, more severe functional deficits, and increased numbers of activated T cells, macrophages, microglial cells, and neutrophils in the affected brain hemisphere of MCAO-treated mu MT(-/-) versus WT mice. These MCAO-induced changes were completely prevented in B-cell-restored mu MT(-/-) mice after transfer of highly purified WT GFP(+) B cells that were detected in the periphery, but not the CNS. In contrast, transfer of B cells from IL-10(-/-) mice had no effect on infarct volume when transferred into mu MT(-/-) mice. These findings strongly support a previously unrecognized activity of IL-10-secreting WT B cells to limit infarct volume, mortality rate, recruitment of inflammatory cells, and functional neurological deficits 48 h after MCAO. Our novel observations are the first to implicate IL-10-secreting B cells as a major regulatory cell type in stroke and suggest that enhancement of regulatory B cells might have application as a novel therapy for this devastating neurologic condition.

关键词： 宫颈癌   调节   B细胞  

摘要： 目的:检测宫颈癌患者外周血调节性B细胞的数量以及血清中IL-10及TGF-β的表达水平,探讨Br1在宫颈癌临床监测中的意义。方法:收集50例宫颈癌患者外周血标本,用间接免疫荧光法检测Br1细胞亚群的分布,用酶联免疫吸附试验(ELISA)检测血清中IL-10及TGF-β的表达情况。结果:宫颈癌患者外周血Br1的数量明显高于正常对照组,IL-10的含量均明显高于正常对照组(P<0.05),宫颈癌浸润组与正常对照组相比,Br1的数量及IL-10明显升高(P<0.05)。结论:宫颈癌患者中Br1的数量及血浆IL-10明显升高,提示Br1细胞与宫颈癌的发生发展可能存在着一定的关系。