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

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 MillerShiv Pillai, Klaus Ley, Catherine C. Hedrick, Coleen A. McNamara

Research output: Contribution to journal › Article › peer-review

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.

Original language	English (US)
Pages (from-to)	1003-1014
Number of pages	12
Journal	Nature Cardiovascular Research
Volume	2
Issue number	11
DOIs	https://doi.org/10.1038/s44161-023-00356-1
State	Published - Nov 2023
Externally published	Yes

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology (miscellaneous)
Cell Biology
Medicine (miscellaneous)
Cardiology and Cardiovascular Medicine

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/s44161-023-00356-1

Cite this

Pattarabanjird, T., Nguyen, A. T., McSkimming, C., Dinh, H. Q., Marshall, M. A., Ghosheh, Y., Gulati, R., Durant, C., Vallejo, J., Saigusa, R., Drago, F., Guy, T. V., Premo, K., Taylor, A. M., Paul, S., Kundu, B., Berr, S., Gonen, A., Tsimikas, S., ... McNamara, C. A. (2023). Human circulating CD24^hi marginal zone B cells produce IgM targeting atherogenic antigens and confer protection from vascular disease. Nature Cardiovascular Research, 2(11), 1003-1014. https://doi.org/10.1038/s44161-023-00356-1

Pattarabanjird, T, Nguyen, AT, McSkimming, C, Dinh, HQ, Marshall, MA, Ghosheh, Y, Gulati, R, Durant, C, Vallejo, J, Saigusa, R, Drago, F, Guy, TV, Premo, K, Taylor, AM, Paul, S, Kundu, B, Berr, S, Gonen, A, Tsimikas, S, Miller, Y, Pillai, S, Ley, K , Hedrick, CC & McNamara, CA 2023, 'Human circulating CD24^hi marginal zone B cells produce IgM targeting atherogenic antigens and confer protection from vascular disease', Nature Cardiovascular Research, vol. 2, no. 11, pp. 1003-1014. https://doi.org/10.1038/s44161-023-00356-1

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

abstract = "IgMs that inactivate oxidation-specific epitopes (IgMOSE), which are secondary products of lipid peroxidization, protect against inflammatory diseases, including diet-induced atherosclerosis. However, the human B cell subtype that produces IgMOSE 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 B27+IgM+CD24hi cells as the major producers of IgMOSE 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 B27+IgM+CD24hi cells (MZB) in patients inversely correlates with coronary artery disease severity.",

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

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AU - Pattarabanjird, Tanyaporn

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AU - McSkimming, Chantel

AU - Dinh, Huy Q.

AU - Marshall, Melissa A.

AU - Ghosheh, Yanal

AU - Gulati, Rishab

AU - Durant, Chistopher

AU - Vallejo, Jenifer

AU - Saigusa, Ryosuke

AU - Drago, Fabrizio

AU - Guy, Thomas V.

AU - Premo, Katherine

AU - Taylor, Angela M.

AU - Paul, Soumen

AU - Kundu, Bijoy

AU - Berr, Stuart

AU - Gonen, Ayelet

AU - Tsimikas, Sotirios

AU - Miller, Yury

AU - Pillai, Shiv

AU - Ley, Klaus

AU - Hedrick, Catherine C.

AU - McNamara, Coleen A.

PY - 2023/11

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N2 - IgMs that inactivate oxidation-specific epitopes (IgMOSE), which are secondary products of lipid peroxidization, protect against inflammatory diseases, including diet-induced atherosclerosis. However, the human B cell subtype that produces IgMOSE 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 B27+IgM+CD24hi cells as the major producers of IgMOSE 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 B27+IgM+CD24hi cells (MZB) in patients inversely correlates with coronary artery disease severity.

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