# Modeling of HIF-1-alpha  Regulation of B Cell Migration

> **NIH NIH R01** · UNIVERSITY OF ROCHESTER · 2021 · $740,364

## Abstract

Project Summary
Characterization of primary human immune responses to infection or vaccination often relies on surveying
peripheral lymphocytes, as access to the sites where primary responses occur, such as the draining lymph
nodes (LN), are not readily accessible due to anatomical location and ethical considerations. Thus, the majority
of studies examining human B cell activation and plasma cell differentiation are performed in vitro under
normoxic tissue culture conditions. However, B cells are activated, differentiate, within the low oxygen germinal
center of the lymph node, and subsequently migrate from one anatomical compartment to another, where they
encounter differing compartmental oxygen levels, ranging from 1-5% in the lymph node to 5-13% in the
peripheral blood. The effects that oxygen levels have on B cells during an active immune response, in particular
migration, is unknown. We hypothesize that oxygen tension is a previously unrecognized B cell regulatory
switch, altering chemokine receptor signaling and controlling B cell migration. To test this hypothesis we
propose the following specific Aims. Aim 1: Define and model the transcriptome and proteome pathways
responsible for O2 dependent functional changes in B cell migratory capacity. Aim 2: Model the overlapping
transcriptome and proteome pathways responsible for calcineurin perturbation of the HIF-1α molecular switch in
human B cells. Aim 3: To assess the in vivo impact HIF-1α stabilization has on vaccine efficacy in a mouse
model of immune suppression. The proposed work is intended to fill a critical gap in our understanding of
human B cell responses, specifically the quantitative effects differing oxygen levels have on B cells migration.

## Key facts

- **NIH application ID:** 10161716
- **Project number:** 5R01AI134058-04
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **Principal Investigator:** Shannon Hilchey
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $740,364
- **Award type:** 5
- **Project period:** 2018-06-06 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10161716

## Citation

> US National Institutes of Health, RePORTER application 10161716, Modeling of HIF-1-alpha  Regulation of B Cell Migration (5R01AI134058-04). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10161716. Licensed CC0.

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