B cell activation during viral infection

描述(申请人提供)：病毒感染是由免疫反应控制的，免疫反应与T淋巴细胞介导的细胞免疫和B淋巴细胞介导的体液免疫有关，T淋巴细胞可以杀死病毒感染的目标并控制病毒的合成，B淋巴细胞产生抗体使病毒灭活。持久抗体反应的存在对于保持对再次感染的抵抗力很重要，也是疫苗设计的一个目标。然而，关于免疫系统激活和动态平衡的研究表明，人们不应该将对病原体的免疫反应视为孤立的独立事件，而是免疫系统中由先前遇到的病原体特有的记忆淋巴细胞池调节的连续体的一部分。先前的T细胞反应影响T细胞对新遇到的病原体的反应的性质，而新遇到的病原体改变了先前遇到的病原体所特有的记忆T细胞池的动态平衡。这种对T细胞反应的调节可以改变病毒的致病机制，是我们所说的异源免疫的一个组成部分，但对于B细胞依赖的抗体反应，异源免疫还没有得到系统的研究。事实上，病毒感染可以增强对以前遇到的病毒的抗体反应，有时还可以增强对自身(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有关的抗体。我们最近的数据显示，无论B细胞免疫球蛋白受体(BCR)的特异性如何，病毒特异性的CD4T细胞在体内对呈递病毒抗原的II类分子上的B细胞产生深远的影响。其中一些B细胞由CD4T细胞裂解，而另一些则被诱导进行多克隆增殖和分化。在这里，我们建议研究非BCR依赖的多克隆B细胞激活现象以及异源病毒感染对体液免疫动态平衡的影响。了解体液免疫是如何维持的，将有助于开发长期保护性疫苗诱导的抗体反应的策略。

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.