puc-header

T-Bet Enables Tissue-Restricted B Cell Memory and Influenza Hemagglutinin Stalk-Specific Antibodies

48 Pages Posted: 25 Oct 2018 Sneak Peek Status: Published

See all articles by Arpita Myles

Arpita Myles

University of Pennsylvania - Department of Pathology and Lab Medicine

James J. Knox

University of Pennsylvania - Department of Pathology and Lab Medicine

Rebecca L. Rosenthal

University of Pennsylvania - Department of Pathology and Lab Medicine

Martin S. Naradikian

La Jolla Institute for Allergy and Immunology (LIAI)

Joanna Madej

University of Pennsylvania - Department of Pathology and Lab Medicine

Mariya Kostiv

University of Pennsylvania - Department of Pathology and Lab Medicine

Scott E. Hensley

University of Pennsylvania - Department of Microbiology

Shannon R. Christensen

University of Pennsylvania - Department of Microbiology

Jonathan Yewdell

National Institutes of Health - Laboratory of Viral Diseases

David H. Canaday

Case Western Reserve University - Division of Infectious Disease

Jinfang Zhu

Government of the United States of America - Laboratory of Immune System Biology

Adrian B. McDermott

Government of the United States of America - Vaccine Research Center

Yoav Dori

University of Pennsylvania - Center for Lymphatic Imaging and Intervention

Max Itkin

University of Pennsylvania - Division of Interventional Radiology

Ali Naji

University of Pennsylvania - Department of Surgery

E. John Wherry

University of Pennsylvania - Institute for Immunology

Michael R. Betts

University of Pennsylvania - Department of Microbiology

Michael P. Cancro

University of Pennsylvania - Department of Pathology and Lab Medicine

More...

Abstract

We describe two functionally distinct influenza hemagglutinin (HA)-specific memory B cell populations (Bmem) in mice and humans, distinguished by T-bet expression. In mice, both T-bet- and T-bet HA-specific B cells emerge within 6 days of influenza infection, persist indefinitely, and transiently express the memory markers CD38, CD73, PD-L2 and CD80. However, while T-bet- Bmem arise in all secondary lymphoid tissues and recirculate, T-bet Bmem neither arise nor migrate within lymphatics, but remain in the spleen. Human HA-specific Bmem display similar features: while T-bet- Bmem are found in all secondary lymphoid tissues, T-bet Bmem are exclusively found in spleen and blood. Using conditional T-bet knockout mice, we show that T-bet B cells are required for the majority of neutralizing and HA stalk-specific IgG2a/c antibodies. Together, these findings show T-bet expression is a durable and conserved feature that discriminates Bmem with distinct origins, tissue distributions, and epitope specificities.

Keywords: Humoral immunity, B cell memory, influenza, T-bet B cells

Suggested Citation

Myles, Arpita and Knox, James J. and Rosenthal, Rebecca L. and Naradikian, Martin S. and Madej, Joanna and Kostiv, Mariya and Hensley, Scott E. and Christensen, Shannon R. and Yewdell, Jonathan and Canaday, David H. and Zhu, Jinfang and McDermott, Adrian B. and Dori, Yoav and Itkin, Max and Naji, Ali and Wherry, E. John and Betts, Michael R. and Cancro, Michael P., T-Bet Enables Tissue-Restricted B Cell Memory and Influenza Hemagglutinin Stalk-Specific Antibodies (October 24, 2018). Available at SSRN: https://ssrn.com/abstract=3272240 or http://dx.doi.org/10.2139/ssrn.3272240
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Arpita Myles

University of Pennsylvania - Department of Pathology and Lab Medicine

34th Street and Civic Center Boulevard
Philadelphia, PA 19104-4399
United States

James J. Knox

University of Pennsylvania - Department of Pathology and Lab Medicine

3400 Spruce St.
Philadelphia, PA 19104-4238
United States

Rebecca L. Rosenthal

University of Pennsylvania - Department of Pathology and Lab Medicine

3400 Spruce St.
Philadelphia, PA 19104-4238
United States

Martin S. Naradikian

La Jolla Institute for Allergy and Immunology (LIAI)

9420 Athena Cir
La Jolla, CA 92037
United States

Joanna Madej

University of Pennsylvania - Department of Pathology and Lab Medicine

3400 Spruce St.
Philadelphia, PA 19104-4238
United States

Mariya Kostiv

University of Pennsylvania - Department of Pathology and Lab Medicine

3400 Spruce St.
Philadelphia, PA 19104-4238
United States

Scott E. Hensley

University of Pennsylvania - Department of Microbiology

Philadelphia, PA 19104
United States

Shannon R. Christensen

University of Pennsylvania - Department of Microbiology

Philadelphia, PA 19104
United States

Jonathan Yewdell

National Institutes of Health - Laboratory of Viral Diseases

Bethesda, MD 20892-9806
United States

David H. Canaday

Case Western Reserve University - Division of Infectious Disease

2511 Overlook Road
Cleveland Heights, OH 44106
United States

Jinfang Zhu

Government of the United States of America - Laboratory of Immune System Biology

Bethesda, MD 20892-9806
United States

Adrian B. McDermott

Government of the United States of America - Vaccine Research Center

Bethesda, MD 20892-9806
United States

Yoav Dori

University of Pennsylvania - Center for Lymphatic Imaging and Intervention

34th Street and Civic Center Boulevard
Philadelphia, PA 19104-4399
United States

Max Itkin

University of Pennsylvania - Division of Interventional Radiology

Philadelphia, PA 19104
United States

Ali Naji

University of Pennsylvania - Department of Surgery

Philadelphia, PA 19104
United States

E. John Wherry

University of Pennsylvania - Institute for Immunology

Philadelphia, PA 19104
United States

Michael R. Betts

University of Pennsylvania - Department of Microbiology

Philadelphia, PA 19104
United States

Michael P. Cancro (Contact Author)

University of Pennsylvania - Department of Pathology and Lab Medicine ( email )

34th Street and Civic Center Boulevard
Philadelphia, PA 19104-4399
United States

Click here to go to Cell.com

Paper statistics

Abstract Views
602
Downloads
32