# Understanding B cell memory in response to diverse virus infections

> **NIH NIH U19** · ROCKEFELLER UNIVERSITY · 2020 · $554,701

## Abstract

ABSTRACT – Project 2, Nussenzweig and Rice
Memory B cells are mediators of immunological memory and vaccine responses. Memory B cells are a
heterogeneous group of cells, that can be distinguished based on phenotypic markers, function, location, the
antibody isotype expressed, and the degree of antibody gene somatic mutation. Our understanding of memory
B cell biology is based primarily on sophisticated experiments using genetically modified mice and model
antigens. In contrast, we know much less about the human memory B cells, in particular about those that develop
in response to a specific pathogen and during natural infection. To date most studies have focused on
sequencing the antibodies from the memory B cells, while many basic aspects of their biology could not be
studied in part due to the difficulty at identifying pathogen-specific cells and their relative paucity. Advances in
single-cell technologies are starting to make these investigations possible.
 In Project 2, the Rice and Nussenzweig laboratories propose to work together to investigate and compare
the B cell memory that develops in response to important human pathogens: the dengue and Zika flaviviruses
(DENV and ZIKV) and the hepatitis B virus (HBV). These viruses are responsible for considerable morbidity and
mortality. More than 40% of the world population lives in areas at risk for infection by DENV and ZIKV flaviviruses
and about 250 million people are living with HBV infection worldwide, despite the existence of an efficacious
HBV vaccine. The immune memory to these pathogens is interesting because it can be either protective (e.g.
HBV vaccination) or potentially harmful (e.g. antibody dependent enhancement of infection with DENV). We
hypothesize that the memory B cells elicited by DENV, ZIKV and HBV in selected individuals are distinct and
characterized by the expression of genes that are either general or pathogen-specific and that are linked to
features of the antibodies that they express. To test this hypothesis, we will combine antigen-specific B cell
purification by cell sorting with single cell transcriptomics analysis. Our approach will take advantage of large
cohorts of human samples obtained through ongoing collaborations with investigators in DENV and ZIKV
endemic areas of Brazil and Mexico, as well as of HBV samples from naturally infected or vaccinated individuals
obtained at the Rockefeller University Hospital.
 Samples from individuals with high DENV and ZIKV neutralizing activity from Brazil and Mexico will be
identified and single memory B cells specific for DENV will be subjected to single cell RNA-seq to characterize
their transcriptome and to obtain paired antibody heavy and light chain sequences (Aim 1). Similarly, we will
analyze single memory B cells elicited by HBV infection or vaccination (Aim 2), and the memory transcriptomes
of DENV, ZIKV and HBV will be compared to each other and to those of naïve B cells. In Aims 3 and 4 we will
clone and character...

## Key facts

- **NIH application ID:** 9884722
- **Project number:** 5U19AI111825-07
- **Recipient organization:** ROCKEFELLER UNIVERSITY
- **Principal Investigator:** Michel C Nussenzweig
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $554,701
- **Award type:** 5
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9884722

## Citation

> US National Institutes of Health, RePORTER application 9884722, Understanding B cell memory in response to diverse virus infections (5U19AI111825-07). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9884722. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*