Human circulating CD24hi marginal zone B cells produce IgM targeting atherogenic antigens and confer protection from vascular disease

Tanyaporn Pattarabanjird; Anh Tram Nguyen; Chantel McSkimming; Huy Q Dinh; Melissa A Marshall; Yanal Ghosheh; Rishab Gulati; Chistopher Durant; Jenifer Vallejo; Ryosuke Saigusa; Fabrizio Drago; Thomas V Guy; Katherine Premo; Angela M Taylor; Soumen Paul; Bijoy Kundu; Stuart Berr; Ayelet Gonen; Sotirios Tsimikas; Yury Miller; Shiv Pillai; Klaus Ley; Catherine C Hedrick; Coleen A McNamara

doi:10.1038/s44161-023-00356-1

Human circulating CD24^hi marginal zone B cells produce IgM targeting atherogenic antigens and confer protection from vascular disease

Nat Cardiovasc Res. 2023 Nov;2(11):1003-1014. doi: 10.1038/s44161-023-00356-1. Epub 2023 Oct 30.

Authors

Tanyaporn Pattarabanjird^{1

2

3

4}, Anh Tram Nguyen², Chantel McSkimming¹, Huy Q Dinh⁵, Melissa A Marshall¹, Yanal Ghosheh⁶, Rishab Gulati⁶, Chistopher Durant⁶, Jenifer Vallejo⁶, Ryosuke Saigusa⁶, Fabrizio Drago^{1

2}, Thomas V Guy⁷, Katherine Premo⁷, Angela M Taylor^{2

4}, Soumen Paul⁸, Bijoy Kundu^{3

8}, Stuart Berr^{3

8}, Ayelet Gonen⁹, Sotirios Tsimikas⁹, Yury Miller⁹, Shiv Pillai⁷, Klaus Ley¹⁰, Catherine C Hedrick¹⁰, Coleen A McNamara^{11

12

13}

Affiliations

¹ Carter Immunology Center, University of Virginia, Charlottesville, VA, USA.
² Cardiovascular Research Center, University of Virginia, Charlottesville, VA, USA.
³ Department of Biomedical Engineering, University of Virginia, Charlottesville, VA, USA.
⁴ Division of Cardiovascular Medicine/Department of Medicine, University of Virginia, Charlottesville, VA, USA.
⁵ McArdle Laboratory for Cancer Research, University of Wisconsin-Madison School of Medicine, Madison, WI, USA.
⁶ La Jolla Institute of Immunology, La Jolla, CA, USA.
⁷ Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
⁸ Department of Radiology and Medical Imaging, University of Virginia, Charlottesville, VA, USA.
⁹ Department of Medicine, University of California, San Diego, La Jolla, CA, USA.
¹⁰ Medical College of Georgia at Augusta University, Augusta, GA, USA.
¹¹ Carter Immunology Center, University of Virginia, Charlottesville, VA, USA. [email protected].
¹² Cardiovascular Research Center, University of Virginia, Charlottesville, VA, USA. [email protected].
¹³ Division of Cardiovascular Medicine/Department of Medicine, University of Virginia, Charlottesville, VA, USA. [email protected].

PMID: 39196097
DOI: 10.1038/s44161-023-00356-1

Abstract

IgMs that inactivate oxidation-specific epitopes (IgM^OSE), which are secondary products of lipid peroxidization, protect against inflammatory diseases, including diet-induced atherosclerosis. However, the human B cell subtype that produces IgM^OSE remains unknown. In this study, we used single-cell mass cytometry and adoptive transfer of B cell subtypes to NOD.Cg-Prkdc^scid Il2rg^tm1Wjl/SzJ (NSG) mice to identify B^{27+IgM+CD24hi} cells as the major producers of IgM^OSE in humans. Notably, these cells have characteristics of human circulatory marginal zone B (MZB) cells, which are known to be atheoroprotective IgM producers in mice. CD24 antibody treatment to reduce MZB cells and IgM in a hyperlipidemic humanized mouse model provides the evidence that MZB cells protect against vascular inflammation. Consistent with these findings, the frequency of B^{27+IgM+CD24hi} cells (MZB) in patients inversely correlates with coronary artery disease severity.

MeSH terms

Adoptive Transfer
Aged
Animals
Atherosclerosis* / immunology
B-Lymphocyte Subsets / immunology
B-Lymphocyte Subsets / metabolism
B-Lymphocytes / immunology
CD24 Antigen* / immunology
CD24 Antigen* / metabolism
Coronary Artery Disease / blood
Coronary Artery Disease / immunology
Disease Models, Animal
Female
Humans
Immunoglobulin M* / immunology
Male
Mice
Mice, Inbred NOD*
Middle Aged

Substances

Immunoglobulin M
CD24 Antigen

Abstract

MeSH terms

Substances

Grants and funding