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Effects of skeletal unloading on the bone marrow antibody repertoire of tetanus toxoid and/or CpG treated C57BL/6J mice.
Life Sciences in Space Research ( IF 2.5 ) Pub Date : 2019-06-14 , DOI: 10.1016/j.lssr.2019.06.001
Trisha A Rettig 1 , Nina C Nishiyama 2 , Michael J Pecaut 2 , Stephen K Chapes 3
Affiliation  

Spaceflight is known to impact the immune system in multiple ways. However, its effect on the antibody repertoire, especially in response to challenge, has not been well characterized. The development of the repertoire has multiple steps that could be affected by spaceflight, including V-(D-)J-gene segment rearrangement and the selection of complementarity determining regions (CDRs); specifically, CDR3, responsible for much of the diversity in the repertoire. We used skeletal unloading with the antiorthostatic suspension (AOS) model to simulate some of the physiological effects associated with spaceflight. Animals ± AOS were challenged with tetanus toxoid (TT) and/or CpG, an adjuvant. Two weeks after challenge, bone marrow was collected and sequenced using the Illumina MiSeq 2 × 300 platform. The resulting antibody repertoire was characterized, including V-, D- (heavy only), and J-gene segment usage, constant region usage, CDR3 length, and V(D)J combinations. We detected changes in gene-segment usage in response to AOS, TT, and CpG treatment in both the heavy and light chains. Additionally, changes were seen in the class-switched VH-gene repertoire. Alterations were also detected in V/J pairing for both the heavy and light chains, and changes in CDR3 length. We also detected lower levels of CDR3 AA overlap than detected in the splenic repertoire. These results demonstrate that AOS, TT, and CpG alter the bone marrow antibody repertoire however, it is still unclear from the data whether there is a loss of host antigen-specific responsiveness because of the change in gene use.



中文翻译:

骨骼负荷对破伤风类毒素和/或CpG治疗的C57BL / 6J小鼠的骨髓抗体库的影响。

众所周知,太空飞行会以多种方式影响免疫系统。但是,其对抗体库的影响,尤其是对攻击的反应,尚未得到很好的表征。曲目的发展有可能受航天影响的多个步骤,包括V-(D-)J基因片段重排和互补决定区(CDR)的选择;具体来说,CDR3负责所有曲目的大部分多样性。我们使用抗体力悬架(AOS)模型进行骨骼卸载,以模拟与航天相关的某些生理效应。用破伤风类毒素(TT)和/或佐剂CpG攻击动物±AOS。攻击后两周,收集骨髓并使用Illumina MiSeq 2×300平台进行测序。表征所得的抗体库,包括V-,D-(仅重)和J基因片段用法,恒定区用法,CDR3长度和V(D)J组合。我们检测到重链和轻链中响应AOS,TT和CpG处理的基因片段使用情况的变化。此外,在类切换的VH基因库中也看到了变化。在重链和轻链的V / J配对中也检测到改变,并且CDR3长度发生了变化。我们还检测到的CDR3 AA重叠水平低于脾脏库中检测到的水平。这些结果表明,AOS,TT和CpG改变了骨髓抗体库,但是,由于基因用途的变化,从数据上是否仍然存在宿主抗原特异性反应能力的丧失仍然不清楚。我们检测到重链和轻链中响应AOS,TT和CpG处理的基因片段使用情况的变化。此外,在类切换的VH基因库中也看到了变化。在重链和轻链的V / J配对中也检测到改变,并且CDR3长度发生了变化。我们还检测到的CDR3 AA重叠水平低于脾脏库中检测到的水平。这些结果表明,AOS,TT和CpG改变了骨髓抗体库,但是,由于基因用途的变化,从数据上是否仍然存在宿主抗原特异性反应能力的丧失仍然不清楚。我们检测到重链和轻链中响应AOS,TT和CpG处理的基因片段使用情况的变化。此外,在类切换的VH基因库中也看到了变化。在重链和轻链的V / J配对中也检测到改变,并且CDR3长度发生了变化。我们还检测到的CDR3 AA重叠水平低于脾脏库中检测到的水平。这些结果表明,AOS,TT和CpG改变了骨髓抗体库,但是,由于基因用途的变化,从数据上是否仍然存在宿主抗原特异性反应能力的丧失仍然不清楚。在重链和轻链的V / J配对中也检测到改变,并且CDR3长度发生了变化。我们还检测到的CDR3 AA重叠水平低于脾脏库中检测到的水平。这些结果表明,AOS,TT和CpG改变了骨髓抗体库,但是,由于基因用途的变化,从数据上是否仍然存在宿主抗原特异性反应能力的丧失仍然不清楚。在重链和轻链的V / J配对中也检测到变化,并且CDR3长度发生变化。我们还检测到的CDR3 AA重叠水平低于脾脏库中检测到的水平。这些结果表明,AOS,TT和CpG改变了骨髓抗体库,但是,由于基因用途的变化,从数据上是否仍然存在宿主抗原特异性反应能力的丧失仍然不清楚。

更新日期:2019-06-14
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