Defining antigen-specific plasmablast and memory B cell subsets in human blood after viral infection or vaccination

被引:290
作者
Ellebedy, Ali H. [1 ,2 ]
Jackson, Katherine J. L. [3 ]
Kissick, Haydn T. [2 ,4 ]
Nakaya, Helder I. [5 ,6 ]
Davis, Carl W. [1 ,2 ]
Roskin, Krishna M. [3 ]
McElroy, Anita K. [7 ,8 ]
Oshansky, Christine M. [9 ]
Elbein, Rivka [10 ]
Thomas, Shine [10 ]
Lyon, George M. [10 ]
Spiropoulou, Christina F. [8 ]
Mehta, Aneesh K. [10 ]
Thomas, Paul G. [9 ]
Boyd, Scott D. [3 ]
Ahmed, Rafi [1 ,2 ]
机构
[1] Emory Univ, Sch Med, Emory Vaccine Ctr, Atlanta, GA USA
[2] Emory Univ, Sch Med, Dept Microbiol & Immunol, Atlanta, GA 30322 USA
[3] Stanford Univ, Dept Pathol, Stanford, CA 94305 USA
[4] Emory Univ, Sch Med, Dept Urol, Atlanta, GA USA
[5] Emory Univ, Sch Med, Dept Pathol, Atlanta, GA 30322 USA
[6] Univ Sao Paulo, Sch Pharmaceut Sci, Dept Clin & Toxicol Anal, Sao Paulo, Brazil
[7] Emory Univ, Sch Med, Dept Pediat, Atlanta, GA USA
[8] US Ctr Dis Control & Prevent, Viral Special Pathogens Branch, Atlanta, GA USA
[9] St Jude Childrens Res Hosp, Dept Immunol, 332 N Lauderdale St, Memphis, TN 38105 USA
[10] Emory Univ, Sch Med, Div Infect Dis, Atlanta, GA USA
基金
美国国家卫生研究院;
关键词
INFLUENZA INFECTION; VIRUS-INFECTION; GENERATION; ANTIBODIES; RESPONSES; NETWORKS;
D O I
10.1038/ni.3533
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Antigen-specific B cells bifurcate into antibody-secreting cells (ASCs) and memory B cells (MBCs) after infection or vaccination. ASCs (plasmablasts) have been extensively studied in humans, but less is known about B cells that become activated but do not differentiate into plasmablasts. Here we have defined the phenotype and transcriptional program of a subset of antigen-specific B cells, which we have called 'activated B cells' (ABCs), that were distinct from ASCs and were committed to the MBC lineage. We detected ABCs in humans after infection with Ebola virus or influenza virus and also after vaccination. By simultaneously analyzing antigen-specific ASCs and ABCs in human blood after vaccination against influenza virus, we investigated the clonal overlap and extent of somatic hypermutation (SHM) in the ASC (effector) and ABC (memory) lineages. Longitudinal tracking of vaccination-induced hemagglutinin (HA)-specific clones revealed no overall increase in SHM over time, which suggested that repeated annual immunization might have limitations in enhancing the quality of influenza-virus-specific antibody.
引用
收藏
页码:1226 / +
页数:11
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