Immunization Elicits Antigen-Specific Antibody Sequestration in Dorsal Root Ganglia Sensory Neurons.

Autor:	Gunasekaran M; Center for Biomedical Science, Feinstein Institute for Medical Research, Northwell Health, Manhasset, NY, United States., Chatterjee PK; Center for Biomedical Science, Feinstein Institute for Medical Research, Northwell Health, Manhasset, NY, United States., Shih A; Center for Genomics and Human Genetics, Feinstein Institute for Medical Research, Northwell Health, Manhasset, NY, United States., Imperato GH; Center for Biomedical Science, Feinstein Institute for Medical Research, Northwell Health, Manhasset, NY, United States.; Elmezzi Graduate School, Feinstein Institute for Medical Research, Northwell Health, Manhasset, NY, United States., Addorisio M; Center for Biomedical Science, Feinstein Institute for Medical Research, Northwell Health, Manhasset, NY, United States., Kumar G; Center for Biomedical Science, Feinstein Institute for Medical Research, Northwell Health, Manhasset, NY, United States.; Elmezzi Graduate School, Feinstein Institute for Medical Research, Northwell Health, Manhasset, NY, United States., Lee A; Center for Genomics and Human Genetics, Feinstein Institute for Medical Research, Northwell Health, Manhasset, NY, United States.; Elmezzi Graduate School, Feinstein Institute for Medical Research, Northwell Health, Manhasset, NY, United States.; Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, United States., Graf JF; GE Global Research Center, Niskayuna, NY, United States., Meyer D; GE Global Research Center, Niskayuna, NY, United States., Marino M; GE Global Research Center, Niskayuna, NY, United States., Puleo C; GE Global Research Center, Niskayuna, NY, United States., Ashe J; GE Global Research Center, Niskayuna, NY, United States., Cox MA; The Campbell Family Institute for Breast Cancer Research, University Health Network, Toronto, ON, Canada., Mak TW; The Campbell Family Institute for Breast Cancer Research, University Health Network, Toronto, ON, Canada., Bouton C; Center for Bioelectronic Medicine, Feinstein Institute for Medical Research, Northwell Health, Manhasset, NY, United States., Sherry B; Elmezzi Graduate School, Feinstein Institute for Medical Research, Northwell Health, Manhasset, NY, United States.; Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, United States.; Center for Immunology and Inflammation, Feinstein Institute for Medical Research, Northwell Health, Manhasset, NY, United States., Diamond B; Elmezzi Graduate School, Feinstein Institute for Medical Research, Northwell Health, Manhasset, NY, United States.; Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, United States.; Center for Autoimmune, Musculoskeletal and Hematopoietic Diseases, Feinstein Institute for Medical Research, Northwell Health, Manhasset, NY, United States., Andersson U; Department of Women's and Children's Health, Karolinska Institutet, Solna, Sweden., Coleman TR; Center for Molecular Innovation, Feinstein Institute for Medical Research, Northwell Health, Manhasset, NY, United States., Metz CN; Center for Biomedical Science, Feinstein Institute for Medical Research, Northwell Health, Manhasset, NY, United States.; Elmezzi Graduate School, Feinstein Institute for Medical Research, Northwell Health, Manhasset, NY, United States.; Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, United States., Tracey KJ; Center for Biomedical Science, Feinstein Institute for Medical Research, Northwell Health, Manhasset, NY, United States.; Elmezzi Graduate School, Feinstein Institute for Medical Research, Northwell Health, Manhasset, NY, United States.; Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, United States.; Center for Bioelectronic Medicine, Feinstein Institute for Medical Research, Northwell Health, Manhasset, NY, United States., Chavan SS; Center for Biomedical Science, Feinstein Institute for Medical Research, Northwell Health, Manhasset, NY, United States.; Elmezzi Graduate School, Feinstein Institute for Medical Research, Northwell Health, Manhasset, NY, United States.; Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, United States.; Center for Bioelectronic Medicine, Feinstein Institute for Medical Research, Northwell Health, Manhasset, NY, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2018 Apr 16; Vol. 9, pp. 638. Date of Electronic Publication: 2018 Apr 16 (Print Publication: 2018).
DOI:	10.3389/fimmu.2018.00638
Abstrakt:	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 1 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.
Databáze:	MEDLINE
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