# Thymic plasma cells as a source of protective natural antibodies in human neonates

> **NIH NIH R21** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2024 · $205,625

## Abstract

PROJECT SUMMARY
Infection is among the leading causes of neonatal deaths worldwide. Serological immunity is considered to be
the most effective first line of defense against endemic pathogens. Understanding how this protective immunity
develops in early life is essential to identify areas of vulnerability and design strategies to combat neonatal
infections worldwide. This area of research however is underexplored. Several recent studies indicate that B cell
immunity starts to develop during fetal life. For instance, cord blood IgM present in the cord blood originate
exclusively from the fetus. Along the same line, IgG from fetal origin is also present in newborns blood although
its exact concentration is masked by the abundance of maternal IgG. Overall, very little is known about the
composition and repertoire of innate humoral immunity developed by the unborn child. The source of these
natural antibodies in the fetus is also unclear. Liver and spleen are important sites of B cell ontogeny in utero but
the differentiation of antibody-producing cells in these two organs during fetal life has not been reported. Our
recent work revealed an alternate and rather unexpected source of natural antibodies in newborns. We
uncovered that the human thymus at birth contains a significant contingent of antibody-producing PC. This
subset is surprisingly heterogenous and includes clones producing all classes and subclasses of immunoglobulin
with the exception of IgD. Furthermore, converging lines of evidence support the view that these PC differentiate
intrathymically through a mechanism that remains to be fully elucidated. Remarkably, ~7% of neonatal PC
reacted to at least 1 of 7 pathogenic and commensal bacteria tested. Neonatal thymic PC were also enriched in
clones reactive to apoptotic cells, a hallmark of natural antibodies. Collectively, these findings exposed the
human thymus as an unsuspected source of natural antibodies in human newborns. Investigating these thymic
PC will therefore provide a rare opportunity to examine how innate humoral immunity develops in humans. Here,
we further characterize the composition of neonatal thymic PC populations and more specifically identify
predominant clones which were more likely to have contributed to innate serological immunity. Studies will also
assess their reactivity profile toward bacteria as well as their protective capabilities. We anticipate these studies
will shed new light on this essential component of natural immune defenses against infections in early life.
Experiments will be carried out in two specific aims:
Aim 1. To characterize Nabs produced by dominant neonatal thymic plasma cells
Aim 2. To assess antibacterial activity of Nabs produced by neonatal thymic plasma cells

## Key facts

- **NIH application ID:** 10738812
- **Project number:** 5R21AI174414-02
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Emmanuel Zorn
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $205,625
- **Award type:** 5
- **Project period:** 2022-11-10 → 2024-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10738812

## Citation

> US National Institutes of Health, RePORTER application 10738812, Thymic plasma cells as a source of protective natural antibodies in human neonates (5R21AI174414-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10738812. Licensed CC0.

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