# Dynamics of Antigen-Driven Selection in Germinal Centers

> **NIH NIH R01** · ROCKEFELLER UNIVERSITY · 2020 · $523,550

## Abstract

7. PROJECT SUMMARY/ABSTRACT
High-affinity antibodies that are protective against infection evolve from lower-affinity precursors in the germinal
center (GC). This evolution is thought to occur by selective expansion of higher-affinity B cell mutants while
lower-affinity ones are eliminated by apoptosis. However, the degree to which affinity-based selection restricts
clonal diversity in the antibody response is unknown, as are the precise kinetics and strength of clonal
evolution in GCs. Thus, we do not know how (or indeed whether) the GC generates the ideal balance between
antibody affinity and clonal diversity necessary for a protective response. This parameter is important to
consider when devising vaccination strategies, especially those aimed at fostering the development of rare B
cell clones with “broadly-neutralizing” potential against HIV and influenza.
This gap in knowledge is largely due to our technical inability to precisely measure clonal diversity and the
strength of selection over time in individual GCs. We have recently developed two microscopy-based
techniques that greatly improve our ability to measure the evolution of clonal diversity during the GC response
in mice: (i) multicolor fate-mapping, which relies on stochastic recombination of a “Brainbow” allele to quantify
the extent of clonal selection in individual GCs by imaging; and (ii) in situ photoactivation, which allows us to
isolate hundreds of B and T cells from individual GCs by flow cytometry. We propose to use these methods to
further our understanding of the role of T cell help in controlling GC clonal diversity, to understand the
difference in clonal dynamics between primary and recall GCs, and to investigate the how clonal dynamics
change over time in chronic GCs induced by retroviral infection. Upon fulfillment of our specific aims, we
expect to have increased our understanding of how clonal competition in GCs affects the diversity and
immunodominance of the antibody response. We expect that our findings will inform future vaccine
development, especially against highly diverse pathogens such as HIV and influenza.

## Key facts

- **NIH application ID:** 9839370
- **Project number:** 5R01AI119006-04
- **Recipient organization:** ROCKEFELLER UNIVERSITY
- **Principal Investigator:** Gabriel D Victora
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $523,550
- **Award type:** 5
- **Project period:** 2017-01-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9839370

## Citation

> US National Institutes of Health, RePORTER application 9839370, Dynamics of Antigen-Driven Selection in Germinal Centers (5R01AI119006-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9839370. Licensed CC0.

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