The duration of antibody responses varies widely with the specific vaccine or infection. The specific features of the immunogen and host responses that are responsible for these differences remain poorly understood. In this application, we describe two transcription factors of the BTB/POZ family which exert opposing effects on the duration of antibody production. The first of these factors, Zbtb20, promotes plasma cell survival and is required for primary long-term antibody responses when aluminum salts, but not Toll-like receptor ligands are used as the adjuvant. The second factor, Zbtb32, promotes plasma cell death and limits the duration of antibody production following memory B cell recall responses, but not primary antibody responses. Based on these findings, we propose to establish the cellular events that explain how adjuvants influence the duration of immunity, and to uncover the physiological consequences to the diversity of antibody responses when recall responses persist for too long. Moreover, we propose to identify the molecular mechanisms of how Zbtb20 and Zbtb32 function to control the duration of humoral immunity.

Public Health Relevance

The length of time that antibodies persist after vaccination and infection and the efficacy of these antibodies against related pathogens varies widely. The goal of this proposal is to identify genetic factors and cellular events that control the duration of immunity after vaccination.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI099108-07
Application #
9616835
Study Section
Cellular and Molecular Immunology - B Study Section (CMIB)
Program Officer
Ferguson, Stacy E
Project Start
2012-09-24
Project End
2022-11-30
Budget Start
2018-12-01
Budget End
2019-11-30
Support Year
7
Fiscal Year
2019
Total Cost
Indirect Cost
Name
University of Arizona
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
806345617
City
Tucson
State
AZ
Country
United States
Zip Code
85721
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Chou, Chun; Verbaro, Daniel J; Tonc, Elena et al. (2016) The Transcription Factor AP4 Mediates Resolution of Chronic Viral Infection through Amplification of Germinal Center B Cell Responses. Immunity 45:570-582
Lam, Wing Y; Becker, Amy M; Kennerly, Krista M et al. (2016) Mitochondrial Pyruvate Import Promotes Long-Term Survival of Antibody-Secreting Plasma Cells. Immunity 45:60-73
Wang, Yinan; Bhattacharya, Deepta (2014) Adjuvant-specific regulation of long-term antibody responses by ZBTB20. J Exp Med 211:841-56
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