Memory B cells, but not long-lived plasma cells, possess antigen specificities for viral escape mutants.
Memory B cells, but not long-lived plasma cells, possess antigen specificities for viral escape mutants.
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记忆B细胞，但没有长寿命的浆细胞具有病毒逃生突变体的抗原特异性。
DOI：
10.1084/jem.20110740
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发表时间：
2011-12-19
期刊：
影响因子：
--
通讯作者：
Diamond MS
中科院分区：
文献类型：
--
作者：
Purtha WE;Tedder TF;Johnson S;Bhattacharya D;Diamond MS
记忆B细胞具有识别西尼罗河病毒变体的独特能力，可能提供对逃避抗体中和的突变病毒的保护。记忆B细胞（MBC）和长寿浆细胞（LLPC）在感染清除后仍然存在，但MBC在随后的保护中所起的特定和非冗余作用尚不清楚。西尼罗河病毒感染小鼠的决议后，我们证明，LLPC是特定的一个单一的显性中和表位，免疫血清抑制差的变异病毒编码在这个关键表位的突变。相比之下，大部分MBC产生的抗体识别野生型（WT）和突变型病毒表位。因此，MBC的多克隆合并物产生的抗体等效地中和WT和变体病毒。值得注意的是，我们还鉴定了比WT蛋白更好地识别突变表位的MBC克隆，尽管从未暴露于变体病毒。通过在二次攻击前过继转移或耗尽MBC的实验证实了MBC在体内应答变异病毒的能力。我们的数据表明，类别转换的MBC可以响应于逃避LLPC产生的抗体中和的原始病原体的变体，而不需要积累额外的体细胞突变。
Memory B cells have the unique capacity to recognize variants of West Nile virus, likely providing protection against mutant viruses that escape antibody neutralization. Memory B cells (MBCs) and long-lived plasma cells (LLPCs) persist after clearance of infection, yet the specific and nonredundant role MBCs play in subsequent protection is unclear. After resolution of West Nile virus infection in mice, we demonstrate that LLPCs were specific for a single dominant neutralizing epitope, such that immune serum poorly inhibited a variant virus that encoded a mutation at this critical epitope. In contrast, a large fraction of MBC produced antibody that recognized both wild-type (WT) and mutant viral epitopes. Accordingly, antibody produced by the polyclonal pool of MBC neutralized WT and variant viruses equivalently. Remarkably, we also identified MBC clones that recognized the mutant epitope better than the WT protein, despite never having been exposed to the variant virus. The ability of MBCs to respond to variant viruses in vivo was confirmed by experiments in which MBCs were adoptively transferred or depleted before secondary challenge. Our data demonstrate that class-switched MBC can respond to variants of the original pathogen that escape neutralization of antibody produced by LLPC without a requirement for accumulating additional somatic mutations.
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DOI：
10.1126/science.1178746
发表时间：
2009-10-09
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Walker LM;Phogat SK;Chan-Hui PY;Wagner D;Phung P;Goss JL;Wrin T;Simek MD;Fling S;Mitcham JL;Lehrman JK;Priddy FH;Olsen OA;Frey SM;Hammond PW;Protocol G Principal Investigators;Kaminsky S;Zamb T;Moyle M;Koff WC;Poignard P;Burton DR
通讯作者：
Burton DR
开发具有针对西尼罗河病毒的治疗潜力的人源化单克隆抗体。
影响因子：
82.9
作者：
Oliphant, Theodore;Engle, Michael;Nybakken, Grant E;Doane, Chris;Johnson, Syd;Huang, Ling;Gorlatov, Sergey;Mehlhop, Erin;Marri, Anantha;Chung, Kyung Min;Ebel, Gregory D;Kramer, Laura D;Fremont, Daved H;Diamond, Michael S
通讯作者：
Diamond, Michael S
影响因子：
3.7
作者：
Corti D;Langedijk JP;Hinz A;Seaman MS;Vanzetta F;Fernandez-Rodriguez BM;Silacci C;Pinna D;Jarrossay D;Balla-Jhagjhoorsingh S;Willems B;Zekveld MJ;Dreja H;O'Sullivan E;Pade C;Orkin C;Jeffs SA;Montefiori DC;Davis D;Weissenhorn W;McKnight A;Heeney JL;Sallusto F;Sattentau QJ;Weiss RA;Lanzavecchia A
通讯作者：
Lanzavecchia A
影响因子：
64.8
作者：
Wrammert, Jens;Smith, Kenneth;Wilson, Patrick C.
通讯作者：
Wilson, Patrick C.
影响因子：
2.2
作者：
Tiller, Thomas;Busse, Christian E.;Wardemann, Hedda
通讯作者：
Wardemann, Hedda