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