Center for Biomedical Science, Feinstein Institute for Medical Research, Northwell Health, Manhasset, NY, United States.
Center for Genomics and Human Genetics, Feinstein Institute for Medical Research, Northwell Health, Manhasset, NY, United States.
Front Immunol. 2018 Apr 16;9:638. doi: 10.3389/fimmu.2018.00638. eCollection 2018.
The immune and nervous systems are two major organ systems responsible for host defense and memory. Both systems achieve memory and learning that can be retained, retrieved, and utilized for decades. Here, we report the surprising discovery that peripheral sensory neurons of the dorsal root ganglia (DRGs) of immunized mice contain antigen-specific antibodies. Using a combination of rigorous molecular genetic analyses, transgenic mice, and adoptive transfer experiments, we demonstrate that DRGs do not synthesize these antigen-specific antibodies, but rather sequester primarily IgG subtype antibodies. As revealed by RNA-seq and targeted quantitative PCR (qPCR), dorsal root ganglion (DRG) sensory neurons harvested from either naïve or immunized mice lack enzymes (i.e., RAG1, RAG2, AID, or UNG) required for generating antibody diversity and, therefore, cannot make antibodies. Additionally, transgenic mice that express a reporter fluorescent protein under the control of Igγ1 constant region fail to express transcripts in DRG sensory neurons. Furthermore, neural sequestration of antibodies occurs in mice rendered deficient in neuronal , but antibody sequestration is not observed in DRG sensory neurons isolated from mice that lack mature B cells [e.g., knock out (KO) or μMT mice]. Finally, adoptive transfer of -deficient bone marrow (BM) into wild-type (WT) mice or WT BM into KO mice revealed that antibody sequestration was observed in DRG sensory neurons of chimeric mice with WT BM but not with -deficient BM. Together, these results indicate that DRG sensory neurons sequester and retain antigen-specific antibodies released by antibody-secreting plasma cells. Coupling this work with previous studies implicating DRG sensory neurons in regulating antigen trafficking during immunization raises the interesting possibility that the nervous system collaborates with the immune system to regulate antigen-mediated responses.
免疫系统和神经系统是负责宿主防御和记忆的两个主要器官系统。这两个系统都能实现记忆和学习，这些记忆和学习可以保留、检索并利用数十年。在这里，我们报告了一个令人惊讶的发现，即免疫小鼠的背根神经节 (DRG) 外周感觉神经元含有抗原特异性抗体。我们使用严格的分子遗传分析、转基因小鼠和过继转移实验的组合，证明 DRG 本身并不合成这些抗原特异性抗体，而是主要隔离 IgG 亚型抗体。如 RNA-seq 和靶向定量 PCR (qPCR) 所示，从未免疫或免疫的小鼠中分离出的背根神经节 (DRG) 感觉神经元缺乏产生抗体多样性所需的酶（即 RAG1、RAG2、AID 或 UNG），因此不能产生抗体。此外，在 Igγ1 恒定区控制下表达报告荧光蛋白的转基因小鼠在 DRG 感觉神经元中未能表达 转录物。此外，在神经元 缺陷的小鼠中发生抗体神经隔离，但在缺乏成熟 B 细胞的小鼠（例如 敲除 (KO) 或 μMT 小鼠）中未观察到 DRG 感觉神经元中的抗体隔离。最后，将 缺陷的骨髓 (BM) 过继转移到野生型 (WT) 小鼠或 WT BM 转移到 KO 小鼠中，结果表明，在具有 WT BM 的嵌合小鼠的 DRG 感觉神经元中观察到抗体隔离，但在缺乏 的 BM 中未观察到抗体隔离。总之，这些结果表明，DRG 感觉神经元隔离并保留由分泌抗体的浆细胞释放的抗原特异性抗体。将这项工作与先前表明 DRG 感觉神经元在免疫过程中调节抗原转运的研究结合起来，提出了一个有趣的可能性，即神经系统与免疫系统合作调节抗原介导的反应。
