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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Antigen-specific antibody responses in B-1a and their relationship to natural immunity
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Antigen-specific antibody responses in B-1a and their relationship to natural immunity

机译：B-1a中抗原特异性抗体应答及其与自然免疫的关系

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B-1a cells are primarily thought of as natural antibody-producing cells. However, we now show that appropriate antigenic stimulation induces IgM and IgG B-1a antibody responses and long-lived T-independent antigen-specific B-1a memory that differs markedly from canonical B-2 humoral immunity. Thus, we show here that in the absence of inflammation, priming with glycolipid (FtL) from Francisella tularensis live vaccine strain induces splenic FtL-specific B-1a to mount dominant IgM and activation-induced cytidine de-aminase-dependent IgG anti-FtL responses that occur within 3-5 d of FtL priming and fade within 1 wk to natural antibody levels that persist indefinitely in the absence of secondary FtL immunization. Equally surprising, FtL priming elicits long-term FtL-specific B-1a memory cells (IgMIgG) that migrate rapidly to the peritoneal cavity and persist there indefinitely, ready to respond to appropriately administrated secondary antigenic stimulation. Unlike B-2 responses, primary FtL-specific B-1a responses and establishment of persistent FtL-specific B-1a memory occur readily in the absence of adjuvants, IL-7, T cells, or germinal center support. However, in another marked departure from the mechanisms controlling B-2 memory responses, rechallenge with FtL in an inflammatory context is required to induce B-1a secondary antibody responses. These findings introduce previously unexplored vaccination strategies for pathogens that target the B-1a repertoire.
机译：B-1a细胞最初被认为是天然产生抗体的细胞。但是，我们现在表明，适当的抗原刺激可诱导IgM和IgG B-1a抗体应答以及长寿的T非依赖性抗原特异性B-1a记忆，这与规范B-2体液免疫明显不同。因此，我们在这里显示，在没有炎症的情况下，使用来自土拉弗朗西斯菌活疫苗株的糖脂（FtL）引发可诱导脾脏FtL特异性B-1a安装占优势的IgM和激活诱导的胞苷脱氨酶依赖性IgG抗FtL对FtL引发3-5 d内发生的反应，并在1周内逐渐消失，直至在没有二次FtL免疫的情况下无限期持续的天然抗体水平。同样令人惊讶的是，FtL引发引发了长期FtL特异性B-1a记忆细胞（IgM IgG），该记忆细胞迅速迁移至腹膜腔并无限期存在，准备对适当给予的次级抗原刺激做出反应。与B-2反应不同，在没有佐剂，IL-7，T细胞或生发中心支持的情况下，原发性FtL特异性B-1a反应和持久性FtL特异性B-1a记忆的建立很容易发生。但是，与控制B-2记忆反应的机制明显不同的是，需要在炎性环境下用FtL进行再刺激才能诱导B-1a二级抗体反应。这些发现为靶向B-1a的病原体引入了以前未曾探索过的疫苗接种策略。

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