# Role of germinal center B cell receptor signaling in positive selection and affinity maturation.

> **NIH NIH F31** · ROCKEFELLER UNIVERSITY · 2020 · $45,520

## Abstract

Abstract
Germinal centers (GCs) play a crucial role in humoral immunity by generating an evolving B cell pool that serves
as the origin of protective memory B and plasma cells. B cell diversification, clonal expansion, and selection in
the GC result in an overall increase in the affinity of serum antibodies for antigen during infection (i.e., affinity
maturation). However, effective affinity maturation requires the enrichment of rare B cells that have acquired
affinity-enhanced mutations for antigen; we now understand that selection of these B cells is controlled by
competition for a limited pool of specialized T follicular helper cells (TFH). Under this T cell centric model, B cell
affinity for Ag is sensed indirectly. However, we still do not understand all the factors that contribute to selection.
A long-standing question has been whether BCR signaling plays a direct role in the selection of high affinity B
cells and affinity maturation. This has proven difficult to study because the intricacies of GC selection dynamics
can only be studied in-vivo, and genetic models compromising components of the BCR signaling pathways
disrupt signaling necessary for GC formation and maintenance. The proposed project addresses these critical
barriers through the development of a tool capable of tracking active BCR signaling in-vivo and novel mouse
models that can be used with pharmacological BCR inhibition. Using these tools, I aim first, to identify and
characterize GC B cells undergoing active BCR signal transduction in-vivo. My second aim is to determine how
BCR signaling affects GC B cell selection to test my overall hypothesis that antigen and T cell derived signals
synergize to drive positive selection and affinity maturation. The outcome of this project will be a molecular
understanding of the role GC BCR signaling plays in the generation of protective antibody responses. These
findings will answer questions central to GC biology and inform future vaccine design.

## Key facts

- **NIH application ID:** 10049956
- **Project number:** 5F31AI147458-02
- **Recipient organization:** ROCKEFELLER UNIVERSITY
- **Principal Investigator:** SPENCER CHEN
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $45,520
- **Award type:** 5
- **Project period:** 2019-07-01 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10049956

## Citation

> US National Institutes of Health, RePORTER application 10049956, Role of germinal center B cell receptor signaling in positive selection and affinity maturation. (5F31AI147458-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10049956. Licensed CC0.

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