Effective vaccines exist for many pathogens. But rational design methods have failed to generate vaccines against many important pathogens. Importantly, our understanding of the molecular pathways involved in generating long-lived and broadly protective immunity is incomplete. Using a newly discovered molecule, this application is directed at understanding pathways that regulate the ability of B cells to provide durable and cross-protective antibody responses. We have discovered that the transcription factor Zbtb20 is required for maintenance of long lived plasma cells, with only high affinity clones persisting afte immunization. These findings provide us with the unique opportunity to: 1) Identify the signaling and survival pathways that regulate plasma cell diversity and lifespan through genetic complementation experiments; 2) Determine the function of low and moderate affinity antibodies in cross-protection against viruses and in the pathogenesis of autoimmunity.

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 and manipulate the molecular mechanisms that regulate both the duration and cross-reactivity of antibody responses after vaccination.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
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Study Section
Cellular and Molecular Immunology - B Study Section (CMIB)
Program Officer
Ferguson, Stacy E
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Washington University
Schools of Medicine
Saint Louis
United States
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Lam, Wing Y; Jash, Arijita; Yao, Cong-Hui et al. (2018) Metabolic and Transcriptional Modules Independently Diversify Plasma Cell Lifespan and Function. Cell Rep 24:2479-2492.e6
Lam, Wing Y; Bhattacharya, Deepta (2018) Metabolic Links between Plasma Cell Survival, Secretion, and Stress. Trends Immunol 39:19-27
Egawa, Takeshi; Bhattacharya, Deepta (2018) Regulation of metabolic supply and demand during B cell activation and subsequent differentiation. Curr Opin Immunol 57:8-14
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