# Hydrogel-based lymphoid tissues for generation of activated human B cells and delivery in vivo

> **NIH NIH R01** · GEORGIA INSTITUTE OF TECHNOLOGY · 2024 · $787,654

## Abstract

Research Summary
Humoral immunity against infections requires the germinal center (GC) differentiation process in the B cell
follicles of lymph nodes. In GCs, naïve B cells rapidly proliferate in response to T cell-dependent
antigen presentation and somatically mutate into high-affinity antibody-secreting cells (plasma cells).
Despite a deep understanding of immunology, numerous challenges exist in understanding disease
transmission, pathology, and developing new vaccines against life-threatening infectious diseases. These
include a limited understanding of immune correlates of protection, identification of viable vaccine candidates,
and off-target effects that must be evaluated in staged clinical trials. Significant pre-clinical research depends
on mice, non-human primates, or other animal models. However, to date, no ex vivo technology has shown
evidence of hallmark GC functional characteristics and the ability to generate high-affinity, long-lived human
plasma and memory B cells. Existing technologies, such as 2D B and T cell co-cultures lead to inefficient GC
responses, and human tonsil transwell aggregates are short-lived. The long-term goal of this project is to
microenvironment that sustains the survival and differentiation of human peripheral blood mononuclear
cells (PBMC)-derived B cells into bona fide human GCs as well as long-lived plasma cells that engraft in vivo.
The central hypothesis is that a synthetic hydrogel-based presentation of cellular and extracellular matrix (ECM)
microenvironmental cues that mimic lymphoid tissues will induce differentiation of human PBMC-derived naïve
B cells into GC B cells and memory cells and prolong the survival of plasma cells ex vivo and in vivo. The central
objective of this project is to understand how the lymphoid microenvironment regulates the ex vivo differentiation
kinetics of human B cells and generate ex vivo long-lived plasma cells that engraft in vivo. The specific aims are:
Aim 1: Bioengineer PEG-4MAL-based lymphoid organoids with human B, T, and stromal cells to recapitulate
temporal kinetics of decision-making of human GC B cells against antigens and adjuvants. Aim 2: Integrate
engineered GCs with forced affinity maturation to isolate high-affinity B cells. Aim 3: Evaluate the in vivo
engraftment of engineered human B cells delivered using injectable gels. This renewal project is highly
significant and innovative because it will 1) engineer a hydrogel-based human immune organoid, inspired by
lymphoid tissues, for generating antigen-specific GC B cells, 2) enable forced affinity maturation ex vivo, and 3)
examine in vivo engraftment of ex vivo engineered B cells.

## Key facts

- **NIH application ID:** 10996228
- **Project number:** 1R01AI186314-01
- **Recipient organization:** GEORGIA INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Ankur Singh
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $787,654
- **Award type:** 1
- **Project period:** 2024-08-01 → 2029-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10996228

## Citation

> US National Institutes of Health, RePORTER application 10996228, Hydrogel-based lymphoid tissues for generation of activated human B cells and delivery in vivo (1R01AI186314-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10996228. Licensed CC0.

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