美国阿拉巴马大学伯明翰分校Frances E. Lund和Anoma Nellore共同合作,近期取得重要工作进展。他们研究发现转录不同的流感特异性效应记忆B细胞亚群可预测人类对疫苗接种的长期抗体反应。相关研究成果2023年3月22日在线发表于《免疫》杂志上。
据介绍,季节性流感疫苗接种可诱导血凝素(HA)特异性记忆B(Bmem)细胞,尽管已经表征了多种Bmem细胞群,但它们之间存在相当大的异质性。
研究人员发现HA特异性人Bmem细胞在表面标记物FcRL5和转录因子T-bet的表达上存在差异。FcRL5+T-bet+Bmem细胞在转录上与效应样记忆细胞相似,而T-betnegFcRL5neg Bmem表现出干细胞样中枢记忆特性。FcRL5+Bmem细胞不表达浆细胞定型因子,但表达转录、表观遗传学、代谢和功能程序,使这些细胞能够产生抗体。
因此,接种后第7天,HA+ T-bet+Bmem细胞表达细胞内免疫球蛋白,扁桃体来源的FcRL5+ Bmem在体外更快地分化为抗体分泌细胞(ASC)。T-bet+ Bmem细胞反应与长寿命体液免疫呈正相关,来自T-bet+ Bmem细胞的克隆类型出现在对重复接种的继发ASC反应中,这表明这种效应子样群体可以预测流感疫苗的持久性和召回潜力。
附:英文原文
Title: A transcriptionally distinct subset of influenza-specific effector memory B cells predicts long-lived antibody responses to vaccination in humans
Author: Anoma Nellore, Esther Zumaquero, Christopher D. Scharer, Christopher F. Fucile, Christopher M. Tipton, R. Glenn King, Tian Mi, Betty Mousseau, John E. Bradley, Fen Zhou, Stuti Mutneja, Paul A. Goepfert, Jeremy M. Boss, Troy D. Randall, Ignacio Sanz, Alexander F. Rosenberg, Frances E. Lund
Issue&Volume: 2023-03-22
Abstract: Seasonal influenza vaccination elicits hemagglutinin (HA)-specific memory B (Bmem)cells, and although multiple Bmem cell populations have been characterized, considerableheterogeneity exists. We found that HA-specific human Bmem cells differed in the expressionof surface marker FcRL5 and transcriptional factor T-bet. FcRL5+T-bet+ Bmem cells were transcriptionally similar to effector-like memory cells, while T-betnegFcRL5neg Bmem cells exhibited stem-like central memory properties. FcRL5+ Bmem cells did not express plasma-cell-commitment factors but did express transcriptional,epigenetic, metabolic, and functional programs that poised these cells for antibodyproduction. Accordingly, HA+ T-bet+ Bmem cells at day 7 post-vaccination expressed intracellular immunoglobulin, andtonsil-derived FcRL5+ Bmem cells differentiated more rapidly into antibody-secreting cells (ASCs) in vitro. The T-bet+ Bmem cell response positively correlated with long-lived humoral immunity, and clonotypesfrom T-bet+ Bmem cells were represented in the secondary ASC response to repeat vaccination,suggesting that this effector-like population predicts influenza vaccine durabilityand recall potential.
DOI: 10.1016/j.immuni.2023.03.001
Source: https://www.cell.com/immunity/fulltext/S1074-7613(23)00094-8
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