# B Cell Subsets in Mouse and Human Atherosclerosis

> **NIH NIH P01** · LA JOLLA INSTITUTE FOR IMMUNOLOGY · 2021 · $366,480

## Abstract

Abstract
B cells have emerged as important immune cells in murine atherosclerosis, regulating lesion development in a
subset-dependent manner. B-2 B cells promote atherosclerosis through poorly defined mechanisms, and B-1 B
cells exert atheroprotective effects largely through production of natural IgM antibodies (NAb). Natural IgM to
oxidation-specific epitopes (OSE) that accumulate in atherosclerosis such as malondialdehyde (MDA) and
phosphorylcholine (PC) present on oxidized low-density lipoprotein can antagonize oxLDL stimulation of
macrophages limiting inflammation. B-1 cells are the major source of circulating IgM in mice. A human
equivalent to the murine B-1 cell was recently identified through its ability to spontaneously produce IgM and
data implicates this cell in producing IgM to OSE on LDL. Plasma levels of IgM to MDA-LDL are associated
with less CAD and fewer CV events in humans. As such, unraveling the pathways that lead to B-1 cell
production of IgM to OSE may enable targeted immune strategies to bolster production of IgM to OSE on LDL
and protect from atherosclerosis in humans. Our work has identified CXCR4 as a key regulator of B-1 NAb
production in mice. Moreover, analyzing a human cohort with intravascular ultrasound (IVUS) to quantify
coronary artery plaque volume, we demonstrate significant association of CXCR4 expression on B-1 cells with
plasma IgM to MDA-LDL and low plaque volume. In this proposal, we will use loss and gain of function studies
in murine atherosclerosis models, and analysis of well characterized human cohorts to study the role of
CXCR4 and other implicated chemokine receptors in mediating B-1 cell atheroprotection.

## Key facts

- **NIH application ID:** 10188607
- **Project number:** 5P01HL136275-05
- **Recipient organization:** LA JOLLA INSTITUTE FOR IMMUNOLOGY
- **Principal Investigator:** Coleen A McNamara
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $366,480
- **Award type:** 5
- **Project period:** 2017-08-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10188607

## Citation

> US National Institutes of Health, RePORTER application 10188607, B Cell Subsets in Mouse and Human Atherosclerosis (5P01HL136275-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10188607. Licensed CC0.

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