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Development of Tbet- and CD11c-Expressing B Cells in a Viral Infection Requires T Follicular Helper Cells Outside of Germinal Centers

65 Pages Posted: 12 Apr 2021 Publication Status: Published

See all articles by Wenzhi Song

Wenzhi Song

Yale University - Department of Immunobiology

Olivia Q. Antao

Rutgers, The State University of New Jersey - Center for Immunity and Inflammation

Emily Condiff

Yale University - Department of Immunobiology

Gina M. Sanchez

Rutgers, The State University of New Jersey - Center for Immunity and Inflammation

Irene Chernova

Yale University - Department of Immunobiology

Krzysztof Zembrzuski

Rutgers, The State University of New Jersey - Center for Immunity and Inflammation

Holly Steach

Yale University - Department of Immunobiology

Kira Rubtsova

National Jewish Health - Department of Biomedical Research

Alexander Lemenze

Rutgers Biomedical Health Sciences - Center for Immunity and Inflammation

Brian J. Laidlaw

Washington University in St. Louis - Division of Allergy and Immunology

Joseph Craft

Yale University - Department of Immunobiology

Jason Weinstein

Rutgers, The State University of New Jersey - Center for Immunity and Inflammation

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Abstract

Tbet+CD11c+ B cells comprise a distinct subset that arises during type 1 pathogen challenge, aging, and autoimmunity in mice and humans. Their developmental reliance upon T cell help and relationship to germinal center (GC) B cells are unclear. We examined Tbet+CD11c+ B cells induced by acute LCMV infections, finding that T follicular helper (Tfh), not T helper 1 (Th1), cells drove their generation prior to GC formation. Genetic fate-tracking and lineage tracing revealed that most Tbet+CD11c+ B cells were not GC-derived and developed independently of cell-intrinsic Bcl6 expression. They localized to the marginal zone where their splenic retention depended upon integrins LFA-1 and VLA-4. After viral clearance, Tbet+CD11c+ B cells formed an uncommon but competitive memory subset, contributing to antibody production and secondary GC seeding upon rechallenge. Therefore, Tbet+CD11c+ B cells are predominantly generated independently of the GC response, yet their development is dependent upon help delivered by Tfh cells.

Suggested Citation

Song, Wenzhi and Antao, Olivia Q. and Condiff, Emily and Sanchez, Gina M. and Chernova, Irene and Zembrzuski, Krzysztof and Steach, Holly and Rubtsova, Kira and Lemenze, Alexander and Laidlaw, Brian J. and Craft, Joseph and Weinstein, Jason, Development of Tbet- and CD11c-Expressing B Cells in a Viral Infection Requires T Follicular Helper Cells Outside of Germinal Centers. Available at SSRN: https://ssrn.com/abstract=3825161 or http://dx.doi.org/10.2139/ssrn.3825161
This version of the paper has not been formally peer reviewed.

Wenzhi Song

Yale University - Department of Immunobiology ( email )

300 Cedar Street
New Haven, CT 06520
United States

Olivia Q. Antao

Rutgers, The State University of New Jersey - Center for Immunity and Inflammation ( email )

United States

Emily Condiff

Yale University - Department of Immunobiology ( email )

300 Cedar Street
New Haven, CT 06520
United States

Gina M. Sanchez

Rutgers, The State University of New Jersey - Center for Immunity and Inflammation ( email )

United States

Irene Chernova

Yale University - Department of Immunobiology ( email )

300 Cedar Street
New Haven, CT 06520
United States

Krzysztof Zembrzuski

Rutgers, The State University of New Jersey - Center for Immunity and Inflammation ( email )

United States

Holly Steach

Yale University - Department of Immunobiology ( email )

300 Cedar Street
New Haven, CT 06520
United States

Kira Rubtsova

National Jewish Health - Department of Biomedical Research

1400 Jackson Street
Denver, CO 80206
United States

Alexander Lemenze

Rutgers Biomedical Health Sciences - Center for Immunity and Inflammation ( email )

United States

Brian J. Laidlaw

Washington University in St. Louis - Division of Allergy and Immunology ( email )

One Brookings Drive
Campus Box 1208
Saint Louis, MO MO 63130-4899
United States

Joseph Craft

Yale University - Department of Immunobiology ( email )

300 Cedar Street
New Haven, CT 06520
United States

Jason Weinstein (Contact Author)

Rutgers, The State University of New Jersey - Center for Immunity and Inflammation ( email )

United States

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