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

May 1, 2020

Contributor: John L Johnson,Rebecca L Rosenthal,James J Knox,Arpita Myles,Martin S Naradikian,Joanna Madej,Mariya Kostiv,Aaron M Rosenfeld,Wenzhao Meng,Shannon R Christensen,Scott E Hensley,Jonathan Yewdell,David H Canaday,Jinfang Zhu,Adrian B McDermott,Yoav Dori,Max Itkin,E John Wherry,Norbert Pardi,Drew Weissman,Ali Naji,Eline T Luning Prak,Michael R Betts,Michael P Cancro

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

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 MBCs and spleen-resident T-bet 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.
Copyright © 2020 Elsevier Inc. All rights reserved.

Author

admin

View all posts

About The Expert

John L Johnson

Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Rebecca L Rosenthal

Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

James J Knox

Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Arpita Myles

Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Martin S Naradikian

La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA.

Joanna Madej

Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Mariya Kostiv

Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Aaron M Rosenfeld

Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Wenzhao Meng

Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Shannon R Christensen

Department of Microbiology, University of Pennsylvania, Philadelphia, PA 19104, USA.

Scott E Hensley

Department of Microbiology, University of Pennsylvania, Philadelphia, PA 19104, USA.

Jonathan Yewdell

Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

David H Canaday

Division of Infectious Disease, Case Western Reserve University School of Medicine, and Cleveland VA Hospital, Cleveland, OH 45106, USA.

Jinfang Zhu

Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

Adrian B McDermott

Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

Yoav Dori

Center for Lymphatic Imaging and Intervention, Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USA.

Max Itkin

Division of Interventional Radiology, Department of Radiology, Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA.

E John Wherry

Institute for Immunology, Parker Institute for Cancer Immunotherapy at University of Pennsylvania, and Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, 19104, USA.

Norbert Pardi

Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Drew Weissman

Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Ali Naji

Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA.

Eline T Luning Prak

Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Michael R Betts

Department of Microbiology, University of Pennsylvania, Philadelphia, PA 19104, USA.

Michael P Cancro

Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: cancro@pennmedicine.upenn.edu.

References

PubMed