# Protective role of B cells in hyperoxic lung injury

> **NIH NIH R03** · MASSACHUSETTS GENERAL HOSPITAL · 2024 · $124,536

## Abstract

High concentrations of inspired oxygen are necessary during treatment of critically ill patients with impaired lung
function, such as those with acute respiratory distress syndrome (ARDS). However, studies in animal models
show that hyperoxia may further exacerbate pulmonary inflammation and compound lung injury. Four-day
exposure of C57BL/6 mice to FiO2>90% leads to diffuse alveolar damage and immune cell infiltration of the
lungs, inclusive of NKT cells and neutrophils. We recently discovered that experimental hyperoxia is associated
with profound loss of pulmonary B cells. Such B cell depletion has also been reported in patients with ARDS.
We now show that adoptive transfer of naïve B cells during hyperoxic exposure not only addresses the B cell
depletion but also limits neutrophil infiltration and decreases the severity of lung injury. Our central hypothesis
for this novel line of investigation is that hyperoxia impacts pulmonary B cell numbers and/or regulatory functions
provoking inflammation. The corollary is that this process can be reversed, and lung injury mitigated by
administration of naïve B cells. We propose that strategies preserving or augmenting B cell numbers in the lungs
could promote immune regulation and mitigate infiltration with inflammatory cell subsets (e.g., NKT cells,
neutrophils) during hyperoxia. In Aim 1, we will characterize the dynamics of B cell responses during hyperoxia
and examine the protective impacts of B cell supplementation. We will also test whether protective effects of
exogenous B cells are mediated by IL-10 or other factors. In Aim 2, we will study mechanistic interactions
between protective B cells and pathogenic NKT cells during hyperoxia as mediated via the autotaxin-
lysophosphatidic acid pathway. We will test whether deletion of NKT cells or inhibition of autotaxin functions
improve B cell numbers in the lungs and/or otherwise enhance protective effects of adoptive B cell
immunotherapy. This R03 award will provide new data on the regulatory role of B cells in hyperoxic lung injury
and ensure essential support to PI Dr. Hanidziar on his path to become an independent, R01 funded investigator.

## Key facts

- **NIH application ID:** 10984706
- **Project number:** 1R03HL171347-01A1
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Dusan Hanidziar
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $124,536
- **Award type:** 1
- **Project period:** 2024-08-01 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10984706

## Citation

> US National Institutes of Health, RePORTER application 10984706, Protective role of B cells in hyperoxic lung injury (1R03HL171347-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10984706. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*