Immunization Elicits Antigen-Specific Antibody Sequestration in Dorsal Root Ganglia Sensory Neurons.
Immunization Elicits Antigen-Specific Antibody Sequestration in Dorsal Root Ganglia Sensory Neurons.
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DOI：
10.3389/fimmu.2018.00638
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发表时间：
2018
影响因子：
7.3
通讯作者：
Chavan SS
中科院分区：
文献类型：
--
作者：
Gunasekaran M;Chatterjee PK;Shih A;Imperato GH;Addorisio M;Kumar G;Lee A;Graf JF;Meyer D;Marino M;Puleo C;Ashe J;Cox MA;Mak TW;Bouton C;Sherry B;Diamond B;Andersson U;Coleman TR;Metz CN;Tracey KJ;Chavan SS
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，可以保留、检索和使用几十年。在这里，我们报告了一个令人惊讶的发现，即免疫小鼠背根神经节（DRGs）的外周感觉神经元含有抗原特异性抗体。使用严格的分子遗传学分析，转基因小鼠和过继转移实验的组合，我们证明，DRG不合成这些抗原特异性抗体，而是主要隔离IgG 1亚型抗体。如通过RNA-seq和靶向定量PCR（qPCR）所揭示的，从幼稚或免疫小鼠收获的背根神经节（DRG）感觉神经元缺乏酶（即，RAG 1、RAG 2、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不能在DRG感觉神经元中表达Ighg 1转录物。此外，在神经元Rag 2缺陷的小鼠中发生抗体的神经隔离，但在从缺乏成熟B细胞的小鼠分离的DRG感觉神经元中未观察到抗体隔离[例如，Rag 1敲除（KO）或μMT小鼠]。最后，过继转移Rag 1缺陷型骨髓（BM）到野生型（WT）小鼠或WT BM到Rag 1 KO小鼠显示，抗体隔离观察到的DRG感觉神经元的嵌合小鼠WT BM，但不是与Rag 1缺陷BM。总之，这些结果表明DRG感觉神经元隔离并保留由抗体分泌浆细胞释放的抗原特异性抗体。将这项工作与先前的研究相结合，涉及DRG感觉神经元在免疫过程中调节抗原运输，提出了神经系统与免疫系统合作调节抗原介导的反应的有趣的可能性。
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 IgG1 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 Ighg1 transcripts in DRG sensory neurons. Furthermore, neural sequestration of antibodies occurs in mice rendered deficient in neuronal Rag2, but antibody sequestration is not observed in DRG sensory neurons isolated from mice that lack mature B cells [e.g., Rag1 knock out (KO) or μMT mice]. Finally, adoptive transfer of Rag1-deficient bone marrow (BM) into wild-type (WT) mice or WT BM into Rag1 KO mice revealed that antibody sequestration was observed in DRG sensory neurons of chimeric mice with WT BM but not with Rag1-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.
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影响因子：
2.4
作者：
Feng B;Bulchand S;Yaksi E;Friedrich RW;Jesuthasan S
通讯作者：
Jesuthasan S
影响因子：
64.5
作者：
CHUN, JJM;SCHATZ, DG;BALTIMORE, D
通讯作者：
BALTIMORE, D
影响因子：
--
作者：
Hanes, William M;Olofsson, Peder S;Tracey, Kevin J
通讯作者：
Tracey, Kevin J
影响因子：
12.3
作者：
Conesa A;Madrigal P;Tarazona S;Gomez-Cabrero D;Cervera A;McPherson A;Szcześniak MW;Gaffney DJ;Elo LL;Zhang X;Mortazavi A
通讯作者：
Mortazavi A
影响因子：
4.8
作者：
Chen, Zhengshan;Gu, Jiang
通讯作者：
Gu, Jiang