# Development and significance of the plasma cell niche in the human infant thymus

> **NIH NIH U01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2021 · $394,144

## Abstract

Project Summary
Our preliminary studies revealed the dynamic evolution of B cell subsets as a function of age in the human
thymus. An initial contingent of medullary B cells present at birth and displaying a phenotype of naive B cells is
progressively replaced by antigen-experienced, antibody-secreting, class-switched plasma cells confined
within the perivascular space (PVS). Plasma cells start to appear in the PVS a few months after birth at a time
that is consistent with early exposure to common endemic viruses and vaccination antigens. We propose that
this latter subset results from previous immunization and constitute an important pool of memory B cells and
plasma cells. The maturing thymus would therefore represent an unrecognized niche for B cell memory
alongside the bone marrow. We also hypothesize that thymic resident plasma cells significantly contribute to
the humoral immunity through their constitutive antibody-secreting capacity. Our proposed studies will use a
large collection of human specimens obtained from donors aged 0-2 years to further characterize this niche
during its early development. Using mice immunized with model antigens, we will then investigate mechanisms
whereby PC accumulate in the thymus and contribute to the overall serum immunity.
Aim 1. To characterize the thymic plasma cell niche in the human infant thymus. We will examine the
kinetics of development of the thymic PC niche in ~250 human thymus specimens from donors aged 0-2 years.
Using immunochemistry, multicolor flow cytometry, gene expression profiling and next generation sequencing-
based IGVH repertoire analysis, we will characterize the architecture, molecular signature and clonal
composition of thymic PC in human infants. A comparison with PC subsets in the spleen and bone marrow of
the same donors will reveal whether thymic PC have unique features.
Aim 2. To determine the reactivity profile of thymic plasma cells in human infants. In aim 2, we will
assess the frequency of thymic PC reactive to a broad range of antigens towards which human infants are
exposed. These include vaccination viral and bacterial antigens, common food antigens as well as ABO blood
group antigens. The possible correlation between antigen-specific B cells in the thymus and the presence of
serum IgG specific to the same antigens will be examined.
Aim 3. To verify the origin of thymic PC and evaluate their role in serological immunity. Mice immunized
with model T cell-dependent and T cell-independent antigens, will be used to verified that thymic PC originate
from peripheral immune responses. We will then use a series of genetically-deficient mouse strains to
investigate the implication of specific chemokines and chemokine receptors as well as survival factors in the
migration and maintenance of thymic PC. Lastly, we will evaluate the capacity of antigen-experienced thymic
PC to confer humoral immunity upon adoptive transfer to or transplantation of thymus fragments under the
renal ...

## Key facts

- **NIH application ID:** 10265678
- **Project number:** 3U01AI131339-05S1
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Emmanuel Zorn
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $394,144
- **Award type:** 3
- **Project period:** 2020-08-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10265678

## Citation

> US National Institutes of Health, RePORTER application 10265678, Development and significance of the plasma cell niche in the human infant thymus (3U01AI131339-05S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10265678. Licensed CC0.

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