The role of CD23+ B cells in human schistosomiasis

CD23 B 细胞在人血吸虫病中的作用

• 批准号: 7569980
• 负责人: LISA M GANLEY-LEAL
• 金额: $ 24.15万
• 依托单位: BOSTON MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-03-01 至 2011-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7569980
• 关键词: Adult; Affect; Antibodies; Antigen Presentation; Antigens; B cell differentiation; B-Cell Activation; B-Lymphocyte Subsets; B-Lymphocytes; Binding; Biology; Blood Vessels; CD19 gene; CXCL13 gene; Cell physiology; Chemotaxis; Cohort Studies; Complex; Data; Developed Countries; Developing Countries; Development; Disease; Flow Cytometry; Future; Generations; Glycoproteins; HIV-1; Helminths; Human; IgE; IgE Receptors; Immune system; Immunity; Immunologics; In Vitro; Individual; Infection; Inflammatory; Knowledge; Lead; Low affinity IgE receptor; Maintenance; Mediating; Morbidity - disease rate; Parasites; Pathway interactions; Phenotype; Platyhelminths; Play; Population; Population Heterogeneity; Population Study; Predisposition; Protein Isoforms; Recording of previous events; Regulation; Resistance; Role; Sampling; Schistosoma; Schistosoma mansoni; Schistosomiasis; Serum; Staging; Structure of germinal center of lymph node; Technology; Tissues; Vaccines; atopy; base; chemotherapy; clinically significant; cohort; crosslink; cytokine; killings; men' s group; monocyte; pathogen; protective effect; research study; vaccine development

DESCRIPTION (provided by applicant): Human schistosomiasis, caused by three main species of tissue invasive parasitic trematodes, currently affects over 207 million individuals and remains a significant cause of morbidity in developing countries. Vaccine development for this disease has been hampered by a poor understanding of the mechanisms involved in protective immunity in humans. Many field-based studies have defined a correlation between high serum concentrations of parasite-specific IgE and resistance to reinfection following curative chemotherapy. The protective effect(s) of IgE remain elusive and may include roles as diverse as direct killing of worms or in regulating immunity. Our preliminary data shows that expression of CD23, the low affinity IgE receptor (Fc5RII), on CD19+ B cells is strongly associated with a history of resistance against S. mansoni in a well- defined cohort of occupationally hyper-exposed Kenyan laborers. We propose to define the role of CD23+ B cells in schistosomiasis by characterizing the specific subsets of B cells that express CD23 and the immunological predictors of CD23 expression. These analyses will be done on circulating B cells and serum samples derived from our well-defined study group of Kenyan laborers using flow cytometry and bead technology. CD23-bound IgE must be cross-linked by antigen to induce B cell activation. Most compelling, there are several antigens synthesized by pathogens which cross-link IgE in a non-antigen specific manner, likely via the Fc region of the antibody, including IPSE/alpha-1, produced by schistosomes. Our preliminary analysis demonstrates that the mechanism by which IgE is cross-linked influences that pathway of B cell differentiation. Whereas antigen-specific CD23-bound IgE cross-linking appears to lead B cells along a pathway of differentiation, non-specific cross-linking reduces activation levels. We hypothesize that IgE has an immunoregulatory role in human schistosomiasis through CD23 expressed on B cells in the development and maintenance of immunity to schistosomes. We plan to determine the effect of differential cross-linking of CD23-bound IgE by schistosome antigens on B cell differentiation and activation using IgE derived from our study population and naove B cells from uninfected donors. We predict that these studies will broaden our knowledge of the potential roles of IgE in protective immunity to schistosomiasis and pave the way for future studies. PUBLIC HEALTH RELEVENCE: Schistosomiasis is a disease that affects 207 million people worldwide and is caused by parasitic flatworms that reside in blood vessels. There is no vaccine because we do not understand how the human immune system is able to kill worms. These studies will delve into the mechanisms involved in human host protection to promote the development of an effective vaccine.

描述（由申请人提供）：人类血吸虫病是由三种主要的组织侵入性寄生虫爆发引起的，目前会影响超过2.07亿个人，并且仍然是发展中国家发病率的重要原因。对人类保护性免疫涉及的机制的不良理解，这种疾病的疫苗开发受到了阻碍。许多基于野外的研究都定义了高血清浓度的寄生虫特异性IgE和治愈化疗后对再感染的抗性之间的相关性。 IgE的保护作用仍然难以捉摸，可能包括直接杀死蠕虫或调节免疫力的角色。我们的初步数据表明，在CD19+ B细胞上的CD23，低亲和力IgE受体（FC5RII）的表达与在良好定义的职业超暴露于肯尼亚劳动者中的抗性史密切相关。我们建议通过表征表达CD23的B细胞的特定子集和CD23表达的免疫学预测指标来定义CD23+ B细胞在血吸虫病中的作用。这些分析将用于使用流式细胞术和珠技术从我们定义明确的肯尼亚劳动者研究组得出的循环B细胞和血清样品。 CD23结合的IgE必须通过抗原交联以诱导B细胞激活。最引人注目的是，有几种由病原体合成的抗原，这些抗原以非抗原特异性方式交联，可能是通过抗体的FC区域（包括IPSE/Alpha-1）的，由schistosomes产生。我们的初步分析表明，IgE与B细胞分化的途径交联的机制。而抗原特异性CD23结合的IgE交联似乎沿分化的途径引导B细胞降低了激活水平。我们假设IgE通过CD23在人类血吸虫病中具有免疫调节作用，该CD23在B细胞的开发和维持对血吸虫的免疫力中表达。我们计划使用源自我们的研究人群和未感染供体的NAOVE B细胞的IgE来确定黑细胞体抗原对CD23结合IgE的差异交联对B细胞分化和激活的影响。我们预测，这些研究将扩大我们对IgE在保护性血吸虫病保护中潜在作用的知识，并为未来的研究铺平道路。公共卫生相关性：血吸虫病是一种影响全球2.07亿人的疾病，是由寄生虫在血管中造成的。没有疫苗，因为我们不了解人类免疫系统如何杀死蠕虫。这些研究将深入研究人类宿主保护涉及的机制，以促进有效疫苗的开发。