B cell activation during viral infection

描述（由申请人提供）：病毒感染由与T淋巴细胞介导的细胞免疫诱导和B淋巴细胞介导的体液免疫相关的免疫反应控制，T淋巴细胞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灭活病毒的抗体。持久抗体反应的存在对于维持对再感染的抵抗力是重要的，也是疫苗设计的目标。然而，对免疫系统激活和体内平衡的研究表明，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，该连续体是由记忆淋巴细胞池对先前遇到的病原体特异性调节的。先前的T细胞反应影响了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记忆T细胞池对先前遇到的病原体的特异性稳态。这种对T细胞反应的调节可以改变病毒的发病机制，是我们所说的异源免疫的一个组成部分，但异源免疫尚未系统地研究过B细胞依赖性抗体反应。事实上，病毒感染可以增强抗体对先前遇到的病毒的反应，有时也可以增强抗体对自身抗原的反应，包括那些与实验性自身免疫性疾病（如糖尿病和红斑狼疮）相关的抗原。我们最近的数据表明，在体内，无论B细胞免疫球蛋白受体（BCR）特异性如何，病毒特异性CD4 T细胞对在其II类分子上呈现病毒抗原的B细胞有深远的影响。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。本文拟探讨bcr非依赖性多克隆B细胞活化现象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，将有助于制定长期保护性疫苗诱导抗体反应的策略。

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.