Characterization of human T-bet-expressing B lymphocytes and their role in the HIV immune response / James J. Knox.

Format:

Book

Manuscript

Thesis/Dissertation

Author/Creator:

Knox, James J., author.

Contributor:

Betts, Michael R., degree supervisor.

Cancro, M. P. (Michael P.), degree committee member.

Hoxie, James A., degree committee member.

Moody, M. A., degree committee member.

Shaw, George M., degree committee member.

Wherry, E. J., degree member.

University of Pennsylvania. Department of Cell and Molecular Biology, degree granting institution.

Language:

English

Subjects (All):

Penn dissertations--Cell and molecular biology.

Cell and molecular biology--Penn dissertations.

Local Subjects:

Penn dissertations--Cell and molecular biology.

Cell and molecular biology--Penn dissertations.

Physical Description:

vii, 100 leaves : illustrations ; 29 cm

Production:

[Philadelphia, Pennsylvania] : University of Pennsylvania, 2017.

Summary:

Humoral immunity is critical for the prevention and control of viral infections, yet the specific B cells and mechanisms regulating antiviral responses in humans remain poorly defined. The Th1-associated transcription factor T-bet coordinates intracellular pathogen immune responses, and recent murine studies identified a T-bet-expressing B cell subset that mediates humoral antiviral immunity, but an analogous cell population has not been identified in humans. In this study, we sought to investigate the role of T-bet-expressing B cells during human viral infections. We identified T-bet expression within the memory B cell compartment of healthy individuals and described a relationship between the transcription factor and IgG1 and IgG3, two antiviral antibody isotypes. The T-bet+ B cell population was comprised of two discrete subsets: T-betlow resting memory cells and a highly activated, transcriptionally distinct T-bethigh subset displaying an atypical memory phenotype. The T-bethigh cell population transiently expanded in blood following vaccination with yellow fever or vaccinia virus; however, these cells were induced and maintained at an elevated frequency by chronic HIV viremia and were associated with increased expression and secretion of IgG1 and IgG3. The HIV gp140-specific response was maintained almost entirely by T-bet+ memory B cells in both viremic and aviremic donors. Together, our findings identify T-bet is a critical regulator of humoral antiviral immunity in humans and suggest T-bet+ B cells specifically mediate the humoral immune responses to live viral vaccines and HIV.

Notes:

Ph. D. University of Pennsylvania 2017.

Department: Cell and Molecular Biology.

Supervisor: Michael R. Betts.

Includes bibliographical references.

OCLC:

1334673973