The Transcription Factor T-bet Resolves Memory B Cell Subsets with Distinct Tissue Distributions and Antibody Specificities in Mice and Humans

被引：152

作者：

Johnson, John L. ^{[1
]}

Rosenthal, Rebecca L. ^{[1
]}

Knox, James J. ^{[1
]}

Myles, Arpita ^{[1
]}

Naradikian, Martin S. ^{[2
]}

Madej, Joanna ^{[1
]}

Kostiv, Mariya ^{[1
]}

Rosenfeld, Aaron M. ^{[1
]}

Meng, Wenzhao ^{[1
]}

Christensen, Shannon R. ^{[3
]}

Hensley, Scott E. ^{[3
]}

Yewdell, Jonathan ^{[4
]}

Canaday, David H. ^{[5
,6
]}

Zhu, Jinfang ^{[7
]}

McDermott, Adrian B. ^{[8
]}

Dori, Yoav ^{[9
]}

Itkin, Max ^{[10
]}

Wherry, E. John ^{[11
,12
]}

Pardi, Norbert ^{[13
]}

Weissman, Drew ^{[13
]}

Naji, Ali ^{[14
]}

Prak, Eline T. Luning ^{[1
]}

Betts, Michael R. ^{[3
]}

Cancro, Michael P. ^{[1
]}

机构：

[1] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA

[2] La Jolla Inst Allergy & Immunol, La Jolla, CA 92037 USA

[3] Univ Penn, Dept Microbiol, Philadelphia, PA 19104 USA

[4] NIAID, Lab Viral Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA

[5] Case Western Reserve Univ, Sch Med, Div Infect Dis, Cleveland, OH 45106 USA

[6] Cleveland VA Hosp, Cleveland, OH 45106 USA

[7] NIAID, Lab Immune Syst Biol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA

[8] NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA

[9] Childrens Hosp Philadelphia, Ctr Lymphat Imaging & Intervent, Philadelphia, PA 19104 USA

[10] Hosp Univ Penn, Dept Radiol, Div Intervent Radiol, 3400 Spruce St, Philadelphia, PA 19104 USA

[11] Univ Penn, Parker Inst Canc Immunotherapy, Inst Immunol, Philadelphia, PA 19104 USA

[12] Univ Penn, Dept Syst Pharmacol & Translat Therapeut, Philadelphia, PA 19104 USA

[13] Univ Penn, Dept Med, Philadelphia, PA 19104 USA

[14] Hosp Univ Penn, Dept Surg, 3400 Spruce St, Philadelphia, PA 19104 USA

来源：

IMMUNITY | 2020年 / 52卷 / 05期

基金：

美国国家卫生研究院;

关键词：

INFLUENZA-VIRUS; EXPRESSION; DIFFERENTIATION; HEMAGGLUTININ; REPERTOIRE; INFECTION; RESPONSES; PATTERNS; PROGRAM; VACCINE;

D O I：

10.1016/j.immuni.2020.03.020

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

B cell subsets expressing the transcription factor T-bet are associated with humoral immune responses and autoimmunity. Here, we examined the anatomic distribution, clonal relationships, and functional properties of T-bet(+) and T-bet(-) memory B cells (MBCs) in the context of the influenza-specific immune response. In mice, both T-bet(-) and T-bet(+) hemagglutinin (HA)-specific B cells arose in germinal centers, acquired memory B cell markers, and persisted indefinitely. Lineage tracing and IgH repertoire analyses revealed minimal interconversion between T-bet(-) and T-bet(+) MBCs, and parabionts showed differential tissue residency and recirculation properties. T-bet(+) MBCs could be subdivided into recirculating T-bet(lo) MBCs and spleen-resident T-bet(hi) MBCs. Human MBCs displayed similar features. Conditional gene deletion studies revealed that T-bet expression in B cells was required for nearly all HA stalk-specific IgG2c antibodies and for durable neutralizing titers to influenza. Thus, T-bet expression distinguishes MBC subsets that have profoundly different homing, residency, and functional properties, and mediate distinct aspects of humoral immune memory.

引用

页码：842 / +

页数：20

共 68 条

[1] The establishment of resident memory B cells in the lung requires local antigen encounter [J].

Allie, S. Rameeza ;

Bradley, John E. ;

Mudunuru, Uma ;

Schultz, Michael D. ;

Graf, Beth A. ;

Lund, Frances E. ;

Randall, Troy D. .

NATURE IMMUNOLOGY, 2019, 20 (01) :97-+

[2] Activation Dynamics and Immunoglobulin Evolution of Pre-existing and Newly Generated Human Memory B cell Responses to Influenza Hemagglutinin [J].

Andrews, Sarah F. ;

Chambers, Michael J. ;

Schramm, Chaim A. ;

Plyler, Jason ;

Raab, Julie E. ;

Kanekiyo, Masaru ;

Gillespie, Rebecca A. ;

Ransier, Amy ;

Darko, Sam ;

Hu, Jianfei ;

Chen, Xuejun ;

Yassine, Hadi M. ;

Boyington, Jeffrey C. ;

Crank, Michelle C. ;

Chen, Grace L. ;

Coates, Emily ;

Mascola, John R. ;

Douek, Daniel C. ;

Graham, Barney S. ;

Ledgerwood, Julie E. ;

McDermott, Adrian B. .

IMMUNITY, 2019, 51 (02) :398-+

[3] Overexpression of T-bet in HIV infection is associated with accumulation of B cells outside germinal centers and poor affinity maturation [J].

Austin, James W. ;

Buckner, Clarisa M. ;

Kardava, Lela ;

Wang, Wei ;

Zhang, Xiaozhen ;

Melson, Valerie A. ;

Swanson, Ryan G. ;

Martins, Andrew J. ;

Zhou, Julian Q. ;

Hoehn, Kenneth B. ;

Fisk, J. Nicholas ;

Dimopoulos, Yiannis ;

Chassiakos, Alexander ;

O'Dell, Sijy ;

Smelkinson, Margery G. ;

Seamon, Catherine A. ;

Kwan, Richard W. ;

Sneller, Michael C. ;

Pittaluga, Stefania ;

Doria-Rose, Nicole A. ;

McDermott, Adrian ;

Li, Yuxing ;

Chun, Tae-Wook ;

Kleinstein, Steven H. ;

Tsang, John S. ;

Petrovas, Constantinos ;

Moir, Susan .

SCIENCE TRANSLATIONAL MEDICINE, 2019, 11 (520)

[4] A Facile Method for the Removal of dsRNA Contaminant from In Vitro-Transcribed mRNA [J].

Baiersdoerfer, Markus ;

Boros, Gabor ;

Muramatsu, Hiromi ;

Mahiny, Azita ;

Vlatkovic, Irena ;

Sahin, Ugur ;

Kariko, Katalin .

MOLECULAR THERAPY-NUCLEIC ACIDS, 2019, 15 :26-35

[5] Cutting Edge: B Cell-Intrinsic T-bet Expression Is Required To Control Chronic Viral Infection [J].

Barnett, Burton E. ;

Staupe, Ryan P. ;

Odorizzi, Pamela M. ;

Palko, Olesya ;

Tomov, Vesselin T. ;

Mahan, Alison E. ;

Gunn, Bronwyn ;

Chen, Diana ;

Paley, Michael A. ;

Alter, Galit ;

Reiner, Steven L. ;

Lauer, Georg M. ;

Teijaro, John R. ;

Wherry, E. John .

JOURNAL OF IMMUNOLOGY, 2016, 197 (04) :1017-1022

[6] A comparative analysis of novel fluorescent proteins as reporters for gene transfer studies [J].

Bell, Peter ;

Vandenberghe, Luk H. ;

Wu, Di ;

Johnston, Julie ;

Limberis, Maria ;

Wilson, James M. .

JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY, 2007, 55 (09) :931-939

[7] Transcriptional insights into the CD8+ T cell response to infection and memory T cell formation [J].

Best, J. Adam ;

Blair, David A. ;

Knell, Jamie ;

Yang, Edward ;

Mayya, Viveka ;

Doedens, Andrew ;

Dustin, Michael L. ;

Goldrath, Ananda W. .

NATURE IMMUNOLOGY, 2013, 14 (04) :404-412

[8] Pulmonary Infection with Influenza A Virus Induces Site-Specific Germinal Center and T Follicular Helper Cell Responses [J].

Boyden, Alexander W. ;

Legge, Kevin L. ;

Waldschmidt, Thomas J. .

PLOS ONE, 2012, 7 (07)

[9]

Branch Alicia, 2012, Morbidity and Mortality Weekly Report, V61, P237

[10] DIVERSITY OF INFLUENZA-SPECIFIC PRIMARY B-CELL REPERTOIRE IN BALB-C MICE [J].

CANCRO, MP ;

GERHARD, W ;

KLINMAN, NR .

JOURNAL OF EXPERIMENTAL MEDICINE, 1978, 147 (03) :776-787

← 1 2 3 4 5 6 7 →