# Molecular control of germinal center selection and affinity maturation

> **NIH NIH R01** · ROCKEFELLER UNIVERSITY · 2021 · $454,516

## Abstract

PROJECT SUMMARY/ABSTRACT
Germinal centers (GCs) are site of antibody somatic hypermutation (SHM) and affinity maturation, and are
therefore essential for effective humoral immune responses to pathogens. Efficient affinity maturation in GCs
requires that B cells cycle between two different cell states, associated with distinct microanacomical
compartments: (i) a “proliferation” mode, when B cells divide and undergo SHM, which takes place in the dark
zone (DZ) of the GC; and (ii) a “selection” mode, when mutated B cells compete with each other based on their
affinity for antigen, which takes place in the GC light zone (LZ). While our previous work defined the
transcriptional programs broadly associated with LZ and DZ states, our understanding of how cells decide
when to transition between one state and another remains incomplete. For example, we do not understand the
signals that trigger DZ B cells to stop proliferating and return to the LZ, nor do we know whether LZ and DZ
cells can be further parsed into additional transcriptionally distinct states that associated with different stages of
GC selection. Here, we propose to combine in vivo models of synchronized GC selection with novel mouse
genetic models, treatment with signaling inhibitors, and single-cell mRNA sequencing to determine the full
complement of GC transcriptional states and to address how these states are associated with GC selection. A
clear definition of these programs will improve our understanding of how GC B cell selection and affinity
maturation are controlled, with implications for vaccine design. Moreover, determining how GC B cell
proliferation is controlled will further our understanding of GC-derived B cell lymphomas, which rely on similar
mechanisms as GCs to achieve sustained proliferation.

## Key facts

- **NIH application ID:** 10212931
- **Project number:** 5R01AI139117-04
- **Recipient organization:** ROCKEFELLER UNIVERSITY
- **Principal Investigator:** Gabriel D Victora
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $454,516
- **Award type:** 5
- **Project period:** 2018-08-15 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10212931

## Citation

> US National Institutes of Health, RePORTER application 10212931, Molecular control of germinal center selection and affinity maturation (5R01AI139117-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10212931. Licensed CC0.

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