B cell activation during viral infection

病毒感染期间 B 细胞激活

• 批准号: 7246733
• 负责人: Raymond M Welsh
• 金额: $ 40.63万
• 依托单位: UNIV OF MASSACHUSETTS MED SCH WORCESTER
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-15 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7246733
• 关键词: Antibodies; Antibody Formation; Antigens; Apoptotic; Autoantigens; Autoimmune Diseases; B-Cell Activation; B-Lymphocytes; CD4 Positive T Lymphocytes; Cells; Cellular Immunity; Class; Cytolysis; Data; Development; Diabetes Mellitus; Event; Goals; Histocompatibility Antigens Class II; Homeostasis; Humoral Immunities; Immune response; Immune system; Immunity; Infection; Infection Control; Light; Lupus; Lymphocyte; Mediating; Memory; Memory Loss; Nature; Proliferating; Resistance; Role; Specificity; T memory cell; T-Lymphocyte; Thinking; Vaccination; Vaccine Design; Viral; Viral Antigens; Viral Pathogenesis; Virus; Virus Diseases; cell killing; cofactor; immunoglobulin receptor; in vivo; killings; lymphocyte proliferation; pathogen; programs; response

DESCRIPTION (provided by applicant): Viral infections are controlled by immune responses associated with the induction of cellular immunity mediated by T lymphocytes, which kill virus-infected targets and control viral synthesis, and of humoral immunity mediated by B lymphocytes, which produce antibodies that inactivate viruses. The presence of long lasting antibody responses is important to maintain resistance to re- infection and is a goal of vaccine design. Studies on immune system activation and homeostasis have shown, however, that one should not think of immune responses to pathogens as isolated independent events, but instead as part of a continuum within an immune system modulated by memory lymphocyte pools specific to previously encountered pathogens. Prior T cell responses influence the nature of T cell responses to newly encountered pathogens, and newly encountered pathogens alter the homeostasis of memory T cell pools specific to previously encountered pathogens. This modulation of T cell responses can alter viral pathogenesis and is a component of what we refer to as heterologous immunity, but heterologous immunity has not been systematically investigated for B cell-dependent antibody responses. In fact, viral infections can enhance antibody responses to previously encountered viruses and sometimes to auto (self) antigens, including those associated with experimental autoimmune diseases like diabetes and lupus erythematosis. Our recent data have demonstrated profound influences in vivo of virus-specific CD4 T cells on B cells presenting viral antigens on their class II molecules, regardless of the B cell immunoglobulin receptor (BCR) specificity. Some of these B cells are lysed by CD4 T cells, whereas others are induced to polyclonally proliferate and differentiate. Here we propose to examine the phenomenon of BCR-independent polyclonal B cell activation and the influence of heterologous viral infections on the homeostasis of humoral immunity. Understanding how humoral immunity is maintained will shed light on strategies for the development of long term protective vaccination-induced antibody responses.

描述（由申请人提供）：病毒感染是通过与 T 淋巴细胞介导的细胞免疫（杀死病毒感染的靶标并控制病毒合成）和 B 淋巴细胞介导的体液免疫（产生抗体）相关的免疫反应来控制的。灭活病毒。持久抗体反应的存在对于维持对再次感染的抵抗力很重要，并且是疫苗设计的目标。然而，关于免疫系统激活和稳态的研究表明，人们不应将对病原体的免疫反应视为孤立的独立事件，而应将其视为免疫系统内连续体的一部分，该免疫系统由针对先前遇到的病原体的记忆淋巴细胞池调节。先前的 T 细胞反应会影响 T 细胞对新遇到的病原体的反应性质，而新遇到的病原体会改变针对先前遇到的病原体的记忆 T 细胞池的稳态。 T 细胞反应的这种调节可以改变病毒的发病机制，并且是我们所说的异源免疫的一个组成部分，但异源免疫尚未针对 B 细胞依赖性抗体反应进行系统研究。事实上，病毒感染可以增强对先前遇到的病毒的抗体反应，有时还可以增强对自身抗原的抗体反应，包括与糖尿病和红斑狼疮等实验性自身免疫性疾病相关的抗体反应。我们最近的数据表明，无论 B 细胞免疫球蛋白受体 (BCR) 特异性如何，体内病毒特异性 CD4 T 细胞对在其 II 类分子上呈递病毒抗原的 B 细胞都有深远的影响。其中一些 B 细胞被 CD4 T 细胞裂解，而另一些则被诱导多克隆增殖和分化。在这里，我们建议研究BCR独立的多克隆B细胞激活现象以及异源病毒感染对体液免疫稳态的影响。了解体液免疫是如何维持的将有助于揭示长期保护性疫苗接种诱导抗体反应的发展策略。