# Project 2: B Cells

> **NIH NIH U54** · STANFORD UNIVERSITY · 2022 · $455,383

## Abstract

PROJECT 2: SUMMARY
The B cell and plasma cell populations that give rise to serum and mucosal antibodies will ultimately determine
the effectiveness and duration of an individual’s humoral immune response to SARS-CoV-2 infection. We will
use several mutually-supporting strategies to analyze these cells in the Boyd lab: single B cell phenotyping, B
cell receptor (BCR) deep sequencing and determination of antigen specificity with DNA-barcoded antigen
tetramers; bulk B cell immunoglobulin gene repertoire sequencing; and monoclonal antibody production from
antigen-specific B cells. In complementary strategy, the Jardetzky lab will make use of yeast display libraries of
patient-derived single-chain antibody variable fragments (ScFv) enriched for native heavy-light chain pairing to
determine the antigen specificity of hundreds to thousands of antigen-specific clones per patient. In longitudinal
peripheral blood samples and nasal biopsy samples we will thoroughly characterize antigen-specific B cell
clones in patient responses to SARS-CoV-2. We hypothesize that with these data we will be able to determine
which features of B cell clonal responses to SARS-CoV-2 are associated with differences in COVID-19 disease
severity and differences between populations groups stratified by age, sex, ethnicity and pre-existing
conditions, or dysregulated immunity in the context of checkpoint blockade treatment. We further hypothesize
that analysis of memory B cell populations together with serological responses may predict which individuals
will have longer-lasting humoral protection against reexposure to SARS-CoV-2. Finally, we will evaluate the B
cell responses stimulated by natural infection compared to vaccination, beginning with the Covaxx peptide-
based vaccine cohort, but with the expectation that additional vaccines will be approved for use during the
period of this project funding. In addition to studying aspects of the B cell responses that differ among these
clinical scenarios, we will search for features such as “convergent” virus-specific BCRs of highly similar
sequences shared between different individuals that may have prognostic value, for example by revealing that
an individual has a potent neutralizing antibody response to SARS-CoV-2. Our Aims are the following:
Specific Aim 1: Analyze B cell responses in acute COVID-19 disease.
Specific Aim 2: Evaluate the formation of B cell memory to SARS-CoV-2.
Specific Aim 3: Analyze mucosal B cell and plasma cell responses to SARS-CoV-2 compared to responses of
B cells in the blood.

## Key facts

- **NIH application ID:** 10688367
- **Project number:** 4U54CA260517-02
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Scott Dexter Boyd
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $455,383
- **Award type:** 4N
- **Project period:** 2020-09-23 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10688367

## Citation

> US National Institutes of Health, RePORTER application 10688367, Project 2: B Cells (4U54CA260517-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10688367. Licensed CC0.

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