B cell activation during viral infection

描述（由申请方提供）：病毒感染通过与T淋巴细胞介导的细胞免疫诱导相关的免疫应答和B淋巴细胞介导的体液免疫诱导相关的免疫应答来控制，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，B淋巴细胞介导的体液免疫产生抗病毒的抗体。持久抗体应答的存在对于维持对再感染的抗性是重要的，并且是疫苗设计的目标。然而，对免疫系统激活和稳态的研究表明，不应将对病原体的免疫应答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，该连续体由对先前遇到的病原体特异性的记忆淋巴细胞库调节。先前的T细胞应答影响T细胞对新遇到的病原体的应答的性质，并且新遇到的病原体改变对先前遇到的病原体特异性的记忆T细胞库的稳态。T细胞应答的这种调节可以改变病毒的发病机制，并且是我们所称的异源免疫的一个组成部分，但是对于B细胞依赖性抗体应答的异源免疫尚未进行系统的研究。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，包括与糖尿病和狼疮性肾炎等实验性自身免疫性疾病相关的抗原。我们最近的数据表明，在体内的病毒特异性的CD4 T细胞对B细胞的深刻影响，提出病毒抗原的II类分子，无论B细胞免疫球蛋白受体（BCR）的特异性。这些B细胞中的一些被CD4 T细胞裂解，而另一些被诱导多克隆增殖和分化。在这里，我们建议检查的现象BCR独立的多克隆B细胞活化和异源病毒感染的体液免疫的稳态的影响。了解体液免疫是如何维持的，将有助于阐明长期保护性疫苗诱导的抗体应答的发展策略。

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.