# Implications of long germinal centers (GC) for T and B cell memory and mucosal immunity

> **NIH NIH U19** · LA JOLLA INSTITUTE FOR IMMUNOLOGY · 2024 · $781,696

## Abstract

PROJECT SUMMARY – Project 1
COVID remains a major killer and disruptor worldwide. We made fundamental contributions to the understanding
of COVID and T and B cell immune memory after SARS2 infection and COVID vaccines. Those studies
predominantly examined human blood. In Project 1 we now aim to complement those fundamental findings with
studies of T and B cell memory of URT lymphoid tissue and nasal epithelium. Mechanistic studies, particularly
in humans, are essential to inform on URT immune memory and the roles of long GCs in adaptive immune
responses, but are currently sparse or nonexistent given the complexities for such experiments. Here we address
these important knowledge gaps, synergizing with Project 2 and 3. We will do so through a series of experiments.
Additionally, there are striking data demonstrating that (1) long GCs can exist after acute SARS2 infection, (2)
long GCs can exist after a protein immunization, and (3) long GCs can exist after mRNA vaccination. The recent
recognition of these long GCs to acute antigens significantly changes our understanding of immune responses,
and long GCs appear to have great value for protective immunity and immune memory. We hypothesize that
long GCs have broad impacts on adaptive immunity, including memory B cell affinity maturation, memory B cell
functional properties, the functionality and durability of memory follicular helper T (TFH) cells, and characteristics
of mucosal immunity in the upper airways. All of those attributes are directly examined in this Project. In both
components (analyses of long GCs and analyses of URT immune memory), we will study multiple human
cohorts, with particular focus on COVID-19 breakthrough infections and COVID-19 vaccinations.

## Key facts

- **NIH application ID:** 10825344
- **Project number:** 2U19AI142742-06
- **Recipient organization:** LA JOLLA INSTITUTE FOR IMMUNOLOGY
- **Principal Investigator:** Shane P Crotty
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $781,696
- **Award type:** 2
- **Project period:** 2019-03-11 → 2029-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10825344

## Citation

> US National Institutes of Health, RePORTER application 10825344, Implications of long germinal centers (GC) for T and B cell memory and mucosal immunity (2U19AI142742-06). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10825344. Licensed CC0.

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