# Tissue and organ specific human B cell immunity

> **NIH NIH U19** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2020 · $3,562,534

## Abstract

Overall: Tissue and organ-specific human B cell immunity
Project Summary
Experiments conducted using genetically modified mice and model pathogens or antigens have shaped our
current understanding of adaptive immunity. From these studies, it is clear that both B and T cell immunity is
exquisitely tailored to the pathogen or antigen. Furthermore, the data show that adaptive immune responses in
lymphoid and peripheral tissues, which are found in both mucosal and systemic sites, can differ dramatically.
Thus, we now know that studying immunity in a single lymphoid tissue to model antigens, while informative, does
not reveal the full complexity of the adaptive immune response. This lesson, learned using mouse models, can
also be applied to human immune responses. To date, the vast majority of human immune responses have only
been queried in the blood. This approach has not only limited our analysis to the lymphocytes that are in
circulation but has also restricted us to examining a small fraction of the cells (typically 1-2%) that are in
circulation at a given time. This “limited sampling approach” has also impaired our capacity to examine antigen-
specific lymphocytes as these cells are rare populations, even during an ongoing immune response, and are
largely undetectable under homeostatic conditions. Thus, we know exceedingly little about the phenotype,
molecular programming, lifespan and function of human immune cells that reside primarily in tissues under
homeostatic conditions. Moreover, we know essentially nothing about the clonal connections between antigen-
specific cells in the different tissues of the human body. These represent fundamental gaps in our basic
knowledge of the human immune system and reduce our ability to design new vaccines to prevent emerging
infections, to create immunotherapies that can be used to treat cancer, autoimmunity and chronic disease and
to develop tolerance-inducing regimens that will improve transplantation outcomes. Therefore, the overall goal
of this U19 Program is to determine the molecular and functional relationships between human memory B
lymphocyte and antibody secreting cell (ASC) populations that are found in pulmonary, intestinal and adipose
tissues under homeostatic conditions. This U19 Program, which is composed of three Projects and three
scientific Cores, will test our central hypothesis that antigen-specific, antigen-experienced human tissue-residing
B cells are heterogeneous with respect to phenotype, transcriptome, breadth of reactivity, and function. We
expect our studies to reveal the identity of novel subsets of antigen-experienced B cells exhibiting unique tissue-
specific “signatures”. This outcome will inform future studies of fundamental basic human immunobiology and is
likely to influence future translational and clinical studies, as B cells specific for the viral antigens and bacterial
cell wall components are important targets for vaccination and are required for host defense against...

## Key facts

- **NIH application ID:** 9882210
- **Project number:** 5U19AI142737-02
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** Frances E. Lund
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $3,562,534
- **Award type:** 5
- **Project period:** 2019-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9882210

## Citation

> US National Institutes of Health, RePORTER application 9882210, Tissue and organ specific human B cell immunity (5U19AI142737-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9882210. Licensed CC0.

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