B-1b Cells Have Unique Functional Traits Compared to B-1a Cells at Homeostasis and in Aged Hyperlipidemic Mice With Atherosclerosis
Immunoglobulin M (IgM) to oxidation specific epitopes (OSE) are inversely associated with atherosclerosis in mice and humans. The B-1b subtype of B-1 cells secrete IgM to OSE, and unlike B-1a cells, are capable of long-lasting IgM memory. What attributes make B-1b cells different than B-1a cells is...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-07-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.909475/full |
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| author | Prasad Srikakulapu Tanyaporn Pattarabanjird Aditi Upadhye Sai Vineela Bontha Victoria Osinski Melissa A. Marshall James Garmey Justine Deroissart Thomas A. Prohaska Joseph L. Witztum Christoph J. Binder Nichol E. Holodick Thomas L. Rothstein Coleen A. McNamara Coleen A. McNamara |
| author_facet | Prasad Srikakulapu Tanyaporn Pattarabanjird Aditi Upadhye Sai Vineela Bontha Victoria Osinski Melissa A. Marshall James Garmey Justine Deroissart Thomas A. Prohaska Joseph L. Witztum Christoph J. Binder Nichol E. Holodick Thomas L. Rothstein Coleen A. McNamara Coleen A. McNamara |
| author_sort | Prasad Srikakulapu |
| collection | DOAJ |
| description | Immunoglobulin M (IgM) to oxidation specific epitopes (OSE) are inversely associated with atherosclerosis in mice and humans. The B-1b subtype of B-1 cells secrete IgM to OSE, and unlike B-1a cells, are capable of long-lasting IgM memory. What attributes make B-1b cells different than B-1a cells is unknown. Our objectives were to determine how B-1b cells produce more IgM compared to B-1a cells at homeostatic condition and to see the differences in the B-1a and B-1b cell distribution and IgM CDR-H3 sequences in mice with advanced atherosclerosis. Here, in-vivo studies demonstrated greater migration to spleen, splenic production of IgM and plasma IgM levels in ApoE-/-Rag1-/- mice intraperitoneally injected with equal numbers of B-1b compared to B-1a cells. Bulk RNA seq analysis and flow cytometry of B-1a and B-1b cells identified CCR6 as a chemokine receptor more highly expressed on B-1b cells compared to B-1a. Knockout of CCR6 resulted in reduced B-1b cell migration to the spleen. Moreover, B-1b cell numbers were significantly higher in spleen of aged atherosclerotic ApoE-/- mice compared to young ApoE-/- mice. Single cell sequencing results of IgHM in B-1a and B-1b cells from peritoneal cavity and spleen of atherosclerotic aged ApoE-/- mice revealed significantly more N additions at the V-D and D-J junctions, greater diversity in V region usage and CDR-H3 sequences in B-1b compared to B-1a cells. In summary, B-1b cells demonstrated enhanced CCR6-mediated splenic migration, IgM production, and IgM repertoire diversification compared to B-1a cells. These findings suggest that potential strategies to selectively augment B-1b cell numbers and splenic trafficking could lead to increased and more diverse IgM targeting OSE to limit atherosclerosis. |
| first_indexed | 2024-04-13T03:36:41Z |
| format | Article |
| id | doaj.art-286501d5bfa64c20ac2f25408827ca76 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-13T03:36:41Z |
| publishDate | 2022-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-286501d5bfa64c20ac2f25408827ca762022-12-22T03:04:19ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-07-011310.3389/fimmu.2022.909475909475B-1b Cells Have Unique Functional Traits Compared to B-1a Cells at Homeostasis and in Aged Hyperlipidemic Mice With AtherosclerosisPrasad Srikakulapu0Tanyaporn Pattarabanjird1Aditi Upadhye2Sai Vineela Bontha3Victoria Osinski4Melissa A. Marshall5James Garmey6Justine Deroissart7Thomas A. Prohaska8Joseph L. Witztum9Christoph J. Binder10Nichol E. Holodick11Thomas L. Rothstein12Coleen A. McNamara13Coleen A. McNamara14Carter Immunology Center, University of Virginia, Charlottesville, VA, United StatesCarter Immunology Center, University of Virginia, Charlottesville, VA, United StatesCardiovascular Research Center, University of Virginia, Charlottesville, VA, United StatesCarter Immunology Center, University of Virginia, Charlottesville, VA, United StatesCardiovascular Research Center, University of Virginia, Charlottesville, VA, United StatesCarter Immunology Center, University of Virginia, Charlottesville, VA, United StatesCarter Immunology Center, University of Virginia, Charlottesville, VA, United StatesDepartment of Laboratory Medicine, Medical University of Vienna, Vienna, AustriaDepartment of Medicine, University of California San Diego, La Jolla, CA, United StatesDepartment of Medicine, University of California San Diego, La Jolla, CA, United StatesDepartment of Laboratory Medicine, Medical University of Vienna, Vienna, AustriaCenter for Immunobiology and Department of Investigative Medicine, Western Michigan University Homer Stryker M.D. School of Medicine, Kalamazoo, MI, United StatesCenter for Immunobiology and Department of Investigative Medicine, Western Michigan University Homer Stryker M.D. School of Medicine, Kalamazoo, MI, United StatesCarter Immunology Center, University of Virginia, Charlottesville, VA, United StatesCardiovascular Division, Department of Medicine, University of Virginia, Charlottesville, VA, United StatesImmunoglobulin M (IgM) to oxidation specific epitopes (OSE) are inversely associated with atherosclerosis in mice and humans. The B-1b subtype of B-1 cells secrete IgM to OSE, and unlike B-1a cells, are capable of long-lasting IgM memory. What attributes make B-1b cells different than B-1a cells is unknown. Our objectives were to determine how B-1b cells produce more IgM compared to B-1a cells at homeostatic condition and to see the differences in the B-1a and B-1b cell distribution and IgM CDR-H3 sequences in mice with advanced atherosclerosis. Here, in-vivo studies demonstrated greater migration to spleen, splenic production of IgM and plasma IgM levels in ApoE-/-Rag1-/- mice intraperitoneally injected with equal numbers of B-1b compared to B-1a cells. Bulk RNA seq analysis and flow cytometry of B-1a and B-1b cells identified CCR6 as a chemokine receptor more highly expressed on B-1b cells compared to B-1a. Knockout of CCR6 resulted in reduced B-1b cell migration to the spleen. Moreover, B-1b cell numbers were significantly higher in spleen of aged atherosclerotic ApoE-/- mice compared to young ApoE-/- mice. Single cell sequencing results of IgHM in B-1a and B-1b cells from peritoneal cavity and spleen of atherosclerotic aged ApoE-/- mice revealed significantly more N additions at the V-D and D-J junctions, greater diversity in V region usage and CDR-H3 sequences in B-1b compared to B-1a cells. In summary, B-1b cells demonstrated enhanced CCR6-mediated splenic migration, IgM production, and IgM repertoire diversification compared to B-1a cells. These findings suggest that potential strategies to selectively augment B-1b cell numbers and splenic trafficking could lead to increased and more diverse IgM targeting OSE to limit atherosclerosis.https://www.frontiersin.org/articles/10.3389/fimmu.2022.909475/fullB-1 cellsIgM antibodiesIgHV sequencingagingCCR6atherosclerosis |
| spellingShingle | Prasad Srikakulapu Tanyaporn Pattarabanjird Aditi Upadhye Sai Vineela Bontha Victoria Osinski Melissa A. Marshall James Garmey Justine Deroissart Thomas A. Prohaska Joseph L. Witztum Christoph J. Binder Nichol E. Holodick Thomas L. Rothstein Coleen A. McNamara Coleen A. McNamara B-1b Cells Have Unique Functional Traits Compared to B-1a Cells at Homeostasis and in Aged Hyperlipidemic Mice With Atherosclerosis Frontiers in Immunology B-1 cells IgM antibodies IgHV sequencing aging CCR6 atherosclerosis |
| title | B-1b Cells Have Unique Functional Traits Compared to B-1a Cells at Homeostasis and in Aged Hyperlipidemic Mice With Atherosclerosis |
| title_full | B-1b Cells Have Unique Functional Traits Compared to B-1a Cells at Homeostasis and in Aged Hyperlipidemic Mice With Atherosclerosis |
| title_fullStr | B-1b Cells Have Unique Functional Traits Compared to B-1a Cells at Homeostasis and in Aged Hyperlipidemic Mice With Atherosclerosis |
| title_full_unstemmed | B-1b Cells Have Unique Functional Traits Compared to B-1a Cells at Homeostasis and in Aged Hyperlipidemic Mice With Atherosclerosis |
| title_short | B-1b Cells Have Unique Functional Traits Compared to B-1a Cells at Homeostasis and in Aged Hyperlipidemic Mice With Atherosclerosis |
| title_sort | b 1b cells have unique functional traits compared to b 1a cells at homeostasis and in aged hyperlipidemic mice with atherosclerosis |
| topic | B-1 cells IgM antibodies IgHV sequencing aging CCR6 atherosclerosis |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.909475/full |
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