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Effects of skeletal unloading on the antibody repertoire of tetanus toxoid and/or CpG treated C57BL/6J mice
Spaceflight affects the immune system, but the effects on the antibody repertoire, responsible for humoral immunity, has not been well explored. In particular, the complex gene assembly and expression process; including mutations, might make this process vulnerable. Complementarity determining regio...
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Published in: | PloS one 2019-01, Vol.14 (1), p.e0210284-e0210284 |
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description | Spaceflight affects the immune system, but the effects on the antibody repertoire, responsible for humoral immunity, has not been well explored. In particular, the complex gene assembly and expression process; including mutations, might make this process vulnerable. Complementarity determining region 3 (CDR3), composed of parts of the V-(D-)J-gene segments, is very important for antigen binding and can be used as an important measure of variability. Skeletal unloading, and the physiological effects of it, parallel many impacts of space flight. Therefore, we explored the impact of skeletal unloading using the antiorthostatic suspension (AOS) model. Animals were experimentally challenged with tetanus toxoid (TT) and/or the adjuvant CpG. Blood was analyzed for anti-TT antibody and corticosterone concentrations. Whole spleen tissue was prepared for repertoire characterization. AOS animals showed higher levels of corticosterone levels, but AOS alone did not affect anti-TT serum antibody levels. Administration of CpG significantly increased the circulating anti-TT antibody concentrations. AOS did alter constant gene usage resulting in higher levels of IgM and lower levels of IgG. CpG also altered constant gene region usage increasing usage of IgA. Significant changes could be detected in multiple V-, D-, and J-gene segments in both the heavy and light chains in response to AOS, TT, and CpG treatments. Analysis of class-switched only transcripts revealed a different pattern of V-gene segment usage than detected in the whole repertoire and also showed significant alterations in gene segment usage after challenge. Alterations in V/J pairing were also detected in response to challenge. CDR3 amino acid sequence overlaps were similar among treatment groups, though the addition of CpG lowered overlap in the heavy chain. We isolated 3,045 whole repertoire and 98 potentially TT-specific CDR3 sequences for the heavy chain and 569 for the light chain. Our results demonstrate that AOS alters the repertoire response to challenge with TT and/or CpG. |
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In particular, the complex gene assembly and expression process; including mutations, might make this process vulnerable. Complementarity determining region 3 (CDR3), composed of parts of the V-(D-)J-gene segments, is very important for antigen binding and can be used as an important measure of variability. Skeletal unloading, and the physiological effects of it, parallel many impacts of space flight. Therefore, we explored the impact of skeletal unloading using the antiorthostatic suspension (AOS) model. Animals were experimentally challenged with tetanus toxoid (TT) and/or the adjuvant CpG. Blood was analyzed for anti-TT antibody and corticosterone concentrations. Whole spleen tissue was prepared for repertoire characterization. AOS animals showed higher levels of corticosterone levels, but AOS alone did not affect anti-TT serum antibody levels. Administration of CpG significantly increased the circulating anti-TT antibody concentrations. AOS did alter constant gene usage resulting in higher levels of IgM and lower levels of IgG. CpG also altered constant gene region usage increasing usage of IgA. Significant changes could be detected in multiple V-, D-, and J-gene segments in both the heavy and light chains in response to AOS, TT, and CpG treatments. Analysis of class-switched only transcripts revealed a different pattern of V-gene segment usage than detected in the whole repertoire and also showed significant alterations in gene segment usage after challenge. Alterations in V/J pairing were also detected in response to challenge. CDR3 amino acid sequence overlaps were similar among treatment groups, though the addition of CpG lowered overlap in the heavy chain. We isolated 3,045 whole repertoire and 98 potentially TT-specific CDR3 sequences for the heavy chain and 569 for the light chain. Our results demonstrate that AOS alters the repertoire response to challenge with TT and/or CpG.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0210284</identifier><identifier>PMID: 30653556</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adjuvants, Immunologic - administration & dosage ; Amino acid sequence ; Animals ; Antibodies ; Antigens ; Astronauts ; Biology ; Biology and Life Sciences ; Biomedical engineering ; Chains ; Change detection ; Complementarity Determining Regions - genetics ; Complementarity-determining region 3 ; Corticosterone ; Corticosterone - blood ; CpG islands ; CpG Islands - immunology ; Female ; Gene expression ; Genes ; Hindlimb Suspension - physiology ; Humoral immunity ; Immune system ; Immunity ; Immunity, Humoral - genetics ; Immunoglobulin A ; Immunoglobulin G ; Immunoglobulin G - blood ; Immunoglobulin Heavy Chains - genetics ; Immunoglobulin Light Chains - genetics ; Immunoglobulin M ; Immunoglobulins ; Immunologic Memory ; Immunology ; Infections ; Light chains ; Medicine and Health Sciences ; Mice ; Mice, Inbred C57BL ; Mutation ; Physiological effects ; Research and Analysis Methods ; Segments ; Signal transduction ; Space Flight ; Spleen ; Tetanus ; Tetanus toxoid ; Tetanus Toxoid - administration & dosage ; Tetanus Toxoid - immunology ; Unloading ; Vaccines ; Weightlessness Simulation</subject><ispartof>PloS one, 2019-01, Vol.14 (1), p.e0210284-e0210284</ispartof><rights>COPYRIGHT 2019 Public Library of Science</rights><rights>2019 Rettig et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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In particular, the complex gene assembly and expression process; including mutations, might make this process vulnerable. Complementarity determining region 3 (CDR3), composed of parts of the V-(D-)J-gene segments, is very important for antigen binding and can be used as an important measure of variability. Skeletal unloading, and the physiological effects of it, parallel many impacts of space flight. Therefore, we explored the impact of skeletal unloading using the antiorthostatic suspension (AOS) model. Animals were experimentally challenged with tetanus toxoid (TT) and/or the adjuvant CpG. Blood was analyzed for anti-TT antibody and corticosterone concentrations. Whole spleen tissue was prepared for repertoire characterization. AOS animals showed higher levels of corticosterone levels, but AOS alone did not affect anti-TT serum antibody levels. Administration of CpG significantly increased the circulating anti-TT antibody concentrations. AOS did alter constant gene usage resulting in higher levels of IgM and lower levels of IgG. CpG also altered constant gene region usage increasing usage of IgA. Significant changes could be detected in multiple V-, D-, and J-gene segments in both the heavy and light chains in response to AOS, TT, and CpG treatments. Analysis of class-switched only transcripts revealed a different pattern of V-gene segment usage than detected in the whole repertoire and also showed significant alterations in gene segment usage after challenge. Alterations in V/J pairing were also detected in response to challenge. CDR3 amino acid sequence overlaps were similar among treatment groups, though the addition of CpG lowered overlap in the heavy chain. We isolated 3,045 whole repertoire and 98 potentially TT-specific CDR3 sequences for the heavy chain and 569 for the light chain. Our results demonstrate that AOS alters the repertoire response to challenge with TT and/or CpG.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>30653556</pmid><doi>10.1371/journal.pone.0210284</doi><tpages>e0210284</tpages><orcidid>https://orcid.org/0000-0003-2833-3096</orcidid><orcidid>https://orcid.org/0000-0001-7434-9182</orcidid><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 1932-6203 |
ispartof | PloS one, 2019-01, Vol.14 (1), p.e0210284-e0210284 |
issn | 1932-6203 1932-6203 |
language | eng |
recordid | cdi_plos_journals_2168175574 |
source | Publicly Available Content Database (Proquest) (PQ_SDU_P3); PubMed Central Free |
subjects | Adjuvants, Immunologic - administration & dosage Amino acid sequence Animals Antibodies Antigens Astronauts Biology Biology and Life Sciences Biomedical engineering Chains Change detection Complementarity Determining Regions - genetics Complementarity-determining region 3 Corticosterone Corticosterone - blood CpG islands CpG Islands - immunology Female Gene expression Genes Hindlimb Suspension - physiology Humoral immunity Immune system Immunity Immunity, Humoral - genetics Immunoglobulin A Immunoglobulin G Immunoglobulin G - blood Immunoglobulin Heavy Chains - genetics Immunoglobulin Light Chains - genetics Immunoglobulin M Immunoglobulins Immunologic Memory Immunology Infections Light chains Medicine and Health Sciences Mice Mice, Inbred C57BL Mutation Physiological effects Research and Analysis Methods Segments Signal transduction Space Flight Spleen Tetanus Tetanus toxoid Tetanus Toxoid - administration & dosage Tetanus Toxoid - immunology Unloading Vaccines Weightlessness Simulation |
title | Effects of skeletal unloading on the antibody repertoire of tetanus toxoid and/or CpG treated C57BL/6J mice |
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