# Biomaterials-based Germinal Center Niches for Understanding the B Cell Maturation and B cell receptor signaling

> **NIH NIH R01** · GEORGIA INSTITUTE OF TECHNOLOGY · 2021 · $367,982

## Abstract

PROJECT SUMMARY
Antibodies are routinely used as therapeutic agents to fight a wide range of disorders including asthma, blood
cancers, breast cancer, arthritis, and transplant rejection. Humoral immunity against infections depends on the
germinal center (GC) differentiation process in the B cell follicles of secondary lymphoid organs, such as
spleen and lymph nodes. In GCs, B cells rapidly proliferate and somatically mutated high-affinity antibody
secreting cells, i.e. plasma cells, are generated from naïve B cells in response to T cell-dependent antigen. To
date, the scientific community has relied on animal models to generate high-affinity antibodies and discover
fundamental knowledge of GC immunology. Yet scientists are far from understanding the extracellular and
intracellular factors that contribute to the exuberant pace of the GC reaction and conversion to antibody
secreting cells (ASCs). Recent in vivo studies have uncovered crucial signals such as CD40 ligand (CD40L)
from T cells, B cell activation factor from follicular dendritic cells, cytokines, and integrin ligands from the
surrounding lymphoid niche, that are required for the induction of GCs and selection of high-affinity cells.
Developing biomaterials to recapitulate the process of generating high affinity, antigen specific antibodies ex
vivo via the GC process could enable more rapid development of antibodies for use in the treatment of a
number of chronic diseases. Such tissue models can also be used to improve the mechanistic investigation
into signaling and epigenetic mechanisms that regulate GC B cells. The goal of this study is not to recapitulate
all aspects of an in vivo model, but rather to generate a model that will inform the natural process in vivo, and
also the development antigen-specific ASCs ex vivo. The specific aims will focus on engineering designer
organoids with tunable ligand specificities, understanding the antigen specific immune response, and establish
a link between integrin ligand specificity and cell cycle epigenetics of GC reaction.

## Key facts

- **NIH application ID:** 10247830
- **Project number:** 5R01AI132738-05
- **Recipient organization:** GEORGIA INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Ankur Singh
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $367,982
- **Award type:** 5
- **Project period:** 2018-02-09 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10247830

## Citation

> US National Institutes of Health, RePORTER application 10247830, Biomaterials-based Germinal Center Niches for Understanding the B Cell Maturation and B cell receptor signaling (5R01AI132738-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10247830. Licensed CC0.

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