Malaria exposure drives both cognate and bystander human B cells to adopt an atypical phenotype.

Malaria exposure drives both cognate and bystander human B cells to adopt an atypical phenotype.
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DOI:
10.1002/eji.201948473
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发表时间:
2020-08
影响因子:
5.4
通讯作者:
Ndungu FM
Ndungu FM
中科院分区:
医学3区
文献类型:
--
作者:
Aye R;Sutton HJ;Nduati EW;Kai O;Mwacharo J;Musyoki J;Otieno E;Wambua J;Bejon P;Cockburn IA;Ndungu FM

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在接触疟疾的人中,发现非典型记忆B细胞(AMBCs)数量增加。一个关键问题是,疟疾是否由于暴露于银或非银特异性机制而导致aMBCs。我们使用四聚体在疟疾既往和持续暴露地区的个体中鉴定了疟原虫和旁观者破伤风类毒素(TT)特异性B细胞。疟疾特异性B细胞比TT特异性B细胞更有可能是aMBCs。然而,来自持续暴露于疟疾的个人的TT特异性B细胞比来自传播已停止的地区的TT特异性B细胞更有可能是aMBCs。最后,特定于血液期疟疾-Ag的BCR序列比来自TT特定BCR的序列发生了更高的突变,并且处于强烈的负选择下,表明持续的抗原压力。我们的数据表明,持续的银暴露和炎症环境都塑造了B细胞对疟疾和旁观者抗原的反应。
Atypical memory B cells (aMBCs) are found in elevated numbers in individuals exposed to malaria. A key question is whether malaria induces aMBCs as a result of exposure to Ag, or non-Ag-specific mechanisms. We identified Plasmodium and bystander tetanus toxoid (TT) specific B cells in individuals from areas of previous and persistent exposure to malaria using tetramers. Malaria-specific B cells were more likely to be aMBCs than TT-specific B cells. However, TT-specific B cells from individuals with continuous exposure to malaria were more likely to be aMBCs than TT-specific B cells in individuals from areas where transmission has ceased. Finally, sequences of BCRs specific for a blood stage malaria-Ag were more highly mutated than sequences from TT-specific BCRs and under strong negative selection, indicative of ongoing antigenic pressure. Our data suggest both persistent Ag exposure and the inflammatory environment shape the B-cell response to malaria and bystander Ags.
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