亲和力受限的记忆B细胞主导异源黄病毒的回忆应
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亲和力受限的记忆B细胞主导异源黄病毒的回忆应

文章来源:美高梅网站>【官网首页】    时间:2020-10-10

本期文章:《免疫》:Online/在线发表

美国亚利桑那大学Deepta Bhattacharya团队发现,亲和力受限的记忆B细胞主导异源黄病毒的回忆应答。2020年10月5日,《免疫》杂志在线发表了这项研究成果。

 

研究人员表示,记忆B细胞(MBC)可以通过次级生发中心(GC)塑造新的特异性,或者选择没有任何亲和力成熟的现有克隆来对异源抗原作出反应。

 

为了区分黄病毒感染和免疫中的这些机制,研究人员测试了对包膜蛋白结构域III(DIII)的回忆应答。在西尼罗河病毒、日本脑炎、寨卡病毒和登革热病毒的异源攻击下,条件性删除激活诱导的胞苷脱氨酶(AID)不会影响回忆应答。DIII特异的MBC大部分包含在偏向浆细胞的CD80+亚群中,在异源加强免疫后很少出现GC,这表明回忆应答受先前存在的克隆多样性的限制。

 

单克隆抗体(mAb)与DIII蛋白的结合亲和力、定时AID缺失、单细胞RNA测序和谱系追踪实验的测试表明,相对亲和力较低的MBC被选择作为促进多样性的机制。工程化免疫原能够避免这种MBC多样性,从而可以促进黄病毒类型特异性疫苗的开发,并使得感染增强的可能性最小化。

 

附:英文原文

 

Title:Affinity-Restricted Memory B Cells Dominate Recall Responses to Heterologous Flaviviruses

 

Author:Rachel Wong Julia A. Belk Jennifer Govero Daved H. Fremont Michael S. Diamond Deepta Bhattacharya

 

Issue&Volume:October 02, 2020

 

Abstract: Memory B cells (MBCs) can respond to heterologous antigens either by molding new specificities through secondary germinal centers (GCs) or by selecting preexisting clones without further affinity maturation. To distinguish these mechanisms in flavivirus infections and immunizations, we studied recall responses to envelope protein domain III (DIII). Conditional deletion of activation-induced cytidine deaminase (AID) between heterologous challenges of West Nile, Japanese encephalitis, Zika, and dengue viruses did not affect recall responses. DIII-specific MBCs were contained mostly within the plasma-cell-biased CD80 + subset, and few GCs arose following heterologous boosters, demonstrating that recall responses are confined by preexisting clonal diversity. Measurement of monoclonal antibody (mAb) binding affinity to DIII proteins, timed AID deletion, single-cell RNA sequencing, and lineage tracing experiments point to selection of relatively low-affinity MBCs as a mechanism to promote diversity. Engineering immunogens to avoid this MBC diversity may facilitate flavivirus-type-specific vaccines with minimized potential for infection enhancement.

 

DOI:https://doi.org/10.1016/j.immuni.2020.09.001

 

Source: https://www.cell.com/immunity/fulltext/S1074-7613(20)30395-2

期刊信息

Immunity:《免疫》,创刊于1994年。隶属于细胞出版社,最新if:21.522
官方网址:https://www.cell.com/immunity/home
投稿链接:https://www.editorialmanager.com/immunity/default.aspx

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