Chemokine Receptor Activation Enhances Memory B Cell Class Switching Linked to IgE Sensitization to Alpha Gal and Cardiovascular Disease
Background: Recent studies have suggested that IgE sensitization to α-gal is associated with coronary artery disease (CAD). However, the B cell subtype(s) responsible for production of IgE to α-gal and mechanisms mediating this production remain elusive.Methods: Single cell multi-omics sequencing, w...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-01-01
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| Series: | Frontiers in Cardiovascular Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcvm.2021.791028/full |
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| author | Tanyaporn Pattarabanjird Tanyaporn Pattarabanjird Tanyaporn Pattarabanjird Jeffrey M. Wilson Loren D. Erickson Loren D. Erickson Lisa J. Workman Hui Qiao Hui Qiao Yanal Ghosheh Rishab Gulati Chistopher Durant Jenifer Vallejo Ryosuke Saigusa Thomas A. E. Platts-Mills Angela M. Taylor Klaus Ley Coleen A. McNamara Coleen A. McNamara Coleen A. McNamara |
| author_facet | Tanyaporn Pattarabanjird Tanyaporn Pattarabanjird Tanyaporn Pattarabanjird Jeffrey M. Wilson Loren D. Erickson Loren D. Erickson Lisa J. Workman Hui Qiao Hui Qiao Yanal Ghosheh Rishab Gulati Chistopher Durant Jenifer Vallejo Ryosuke Saigusa Thomas A. E. Platts-Mills Angela M. Taylor Klaus Ley Coleen A. McNamara Coleen A. McNamara Coleen A. McNamara |
| author_sort | Tanyaporn Pattarabanjird |
| collection | DOAJ |
| description | Background: Recent studies have suggested that IgE sensitization to α-gal is associated with coronary artery disease (CAD). However, the B cell subtype(s) responsible for production of IgE to α-gal and mechanisms mediating this production remain elusive.Methods: Single cell multi-omics sequencing, was utilized to phenotype B cells obtained from 60 subjects that had undergone coronary angiography in whom serum IgE was evaluated by ImmunoCAP. Bioinformatics approaches were used to identify B cell subtype(s) and transcriptomic signatures associated with α-gal sensitization. In vitro characterization of chemokine/chemokine receptor pairs on switched memory B cells associated with IgE to α-gal was performed.Results: Of the 60 patients, 17 (28%) were positive for IgE to α-gal. CITESeq identified CCR6+ class-switched memory (SWM) B cells and CXCR4 expresssion on these CCR6+ SWM B cells as significantly associated with IgE sensitization to α-gal but not to other common allergens (peanut or inhalants). In vitro studies of enriched human B cells revealed significantly greater IgE on SWM B cells with high CCR6 and CXCR4 expression 10 days after cells were treated with IL-4 and CD40 to stimulate class switch recombination. Both CCL20 (CCR6 ligand) and CXCL12 (ligand for CXCR4) increased the expression of IgE on SWM B cells expressing their receptors. However, they appeared to have unique pathways mediating this effect as only CCL20 increased activation-induced cytidine deaminase (AID), while CXCL12 drove proliferation of CXCR4+ SWM B cells. Lastly, correlation analysis indicated an association between CAD severity and the frequency of both CCR6+ SWM and CXCR4+ SWM B cells.Conclusions: CCR6+ SWM B cells were identified as potential producers of IgE to α-gal in CAD patients. Additionally, our findings highlighted non-chemotaxis roles of CCL20/CCR6 and CXCL12/CXCR4 signaling in mediating IgE class switching and cell proliferation of SWM B cells respectively. Results may have important implications for a better understanding and better therapeutic approaches for subjects with IgE sensitization to α-gal. |
| first_indexed | 2024-12-18T05:35:03Z |
| format | Article |
| id | doaj.art-fdd20fd874ad4accbfddcc64261a926c |
| institution | Directory Open Access Journal |
| issn | 2297-055X |
| language | English |
| last_indexed | 2024-12-18T05:35:03Z |
| publishDate | 2022-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cardiovascular Medicine |
| spelling | doaj.art-fdd20fd874ad4accbfddcc64261a926c2022-12-21T21:19:20ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2022-01-01810.3389/fcvm.2021.791028791028Chemokine Receptor Activation Enhances Memory B Cell Class Switching Linked to IgE Sensitization to Alpha Gal and Cardiovascular DiseaseTanyaporn Pattarabanjird0Tanyaporn Pattarabanjird1Tanyaporn Pattarabanjird2Jeffrey M. Wilson3Loren D. Erickson4Loren D. Erickson5Lisa J. Workman6Hui Qiao7Hui Qiao8Yanal Ghosheh9Rishab Gulati10Chistopher Durant11Jenifer Vallejo12Ryosuke Saigusa13Thomas A. E. Platts-Mills14Angela M. Taylor15Klaus Ley16Coleen A. McNamara17Coleen A. McNamara18Coleen A. McNamara19Carter Immunology Center, University of Virginia, Charlottesville, VA, United StatesCardiovascular Research Center, University of Virginia, Charlottesville, VA, United StatesDepartment of Biomedical Engineering, University of Virginia, Charlottesville, VA, United StatesDivision of Allergy and Immunology, Department of Medicine, University of Virginia, Charlottesville, VA, United StatesCarter Immunology Center, University of Virginia, Charlottesville, VA, United StatesDepartment of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, VA, United StatesDivision of Allergy and Immunology, Department of Medicine, University of Virginia, Charlottesville, VA, United StatesCarter Immunology Center, University of Virginia, Charlottesville, VA, United StatesDepartment of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, VA, United StatesLa Jolla Institute of Immunology, La Jolla, CA, United StatesLa Jolla Institute of Immunology, La Jolla, CA, United StatesLa Jolla Institute of Immunology, La Jolla, CA, United StatesLa Jolla Institute of Immunology, La Jolla, CA, United StatesLa Jolla Institute of Immunology, La Jolla, CA, United StatesDivision of Allergy and Immunology, Department of Medicine, University of Virginia, Charlottesville, VA, United StatesDivision of Cardiovascular Medicine, Department of Medicine, University of Virginia, Charlottesville, VA, United StatesLa Jolla Institute of Immunology, La Jolla, CA, United StatesCarter Immunology Center, University of Virginia, Charlottesville, VA, United StatesCardiovascular Research Center, University of Virginia, Charlottesville, VA, United StatesDivision of Cardiovascular Medicine, Department of Medicine, University of Virginia, Charlottesville, VA, United StatesBackground: Recent studies have suggested that IgE sensitization to α-gal is associated with coronary artery disease (CAD). However, the B cell subtype(s) responsible for production of IgE to α-gal and mechanisms mediating this production remain elusive.Methods: Single cell multi-omics sequencing, was utilized to phenotype B cells obtained from 60 subjects that had undergone coronary angiography in whom serum IgE was evaluated by ImmunoCAP. Bioinformatics approaches were used to identify B cell subtype(s) and transcriptomic signatures associated with α-gal sensitization. In vitro characterization of chemokine/chemokine receptor pairs on switched memory B cells associated with IgE to α-gal was performed.Results: Of the 60 patients, 17 (28%) were positive for IgE to α-gal. CITESeq identified CCR6+ class-switched memory (SWM) B cells and CXCR4 expresssion on these CCR6+ SWM B cells as significantly associated with IgE sensitization to α-gal but not to other common allergens (peanut or inhalants). In vitro studies of enriched human B cells revealed significantly greater IgE on SWM B cells with high CCR6 and CXCR4 expression 10 days after cells were treated with IL-4 and CD40 to stimulate class switch recombination. Both CCL20 (CCR6 ligand) and CXCL12 (ligand for CXCR4) increased the expression of IgE on SWM B cells expressing their receptors. However, they appeared to have unique pathways mediating this effect as only CCL20 increased activation-induced cytidine deaminase (AID), while CXCL12 drove proliferation of CXCR4+ SWM B cells. Lastly, correlation analysis indicated an association between CAD severity and the frequency of both CCR6+ SWM and CXCR4+ SWM B cells.Conclusions: CCR6+ SWM B cells were identified as potential producers of IgE to α-gal in CAD patients. Additionally, our findings highlighted non-chemotaxis roles of CCL20/CCR6 and CXCL12/CXCR4 signaling in mediating IgE class switching and cell proliferation of SWM B cells respectively. Results may have important implications for a better understanding and better therapeutic approaches for subjects with IgE sensitization to α-gal.https://www.frontiersin.org/articles/10.3389/fcvm.2021.791028/fullalpha-galB cellscoronary artery diseaseIgE class switchingCITESeq |
| spellingShingle | Tanyaporn Pattarabanjird Tanyaporn Pattarabanjird Tanyaporn Pattarabanjird Jeffrey M. Wilson Loren D. Erickson Loren D. Erickson Lisa J. Workman Hui Qiao Hui Qiao Yanal Ghosheh Rishab Gulati Chistopher Durant Jenifer Vallejo Ryosuke Saigusa Thomas A. E. Platts-Mills Angela M. Taylor Klaus Ley Coleen A. McNamara Coleen A. McNamara Coleen A. McNamara Chemokine Receptor Activation Enhances Memory B Cell Class Switching Linked to IgE Sensitization to Alpha Gal and Cardiovascular Disease Frontiers in Cardiovascular Medicine alpha-gal B cells coronary artery disease IgE class switching CITESeq |
| title | Chemokine Receptor Activation Enhances Memory B Cell Class Switching Linked to IgE Sensitization to Alpha Gal and Cardiovascular Disease |
| title_full | Chemokine Receptor Activation Enhances Memory B Cell Class Switching Linked to IgE Sensitization to Alpha Gal and Cardiovascular Disease |
| title_fullStr | Chemokine Receptor Activation Enhances Memory B Cell Class Switching Linked to IgE Sensitization to Alpha Gal and Cardiovascular Disease |
| title_full_unstemmed | Chemokine Receptor Activation Enhances Memory B Cell Class Switching Linked to IgE Sensitization to Alpha Gal and Cardiovascular Disease |
| title_short | Chemokine Receptor Activation Enhances Memory B Cell Class Switching Linked to IgE Sensitization to Alpha Gal and Cardiovascular Disease |
| title_sort | chemokine receptor activation enhances memory b cell class switching linked to ige sensitization to alpha gal and cardiovascular disease |
| topic | alpha-gal B cells coronary artery disease IgE class switching CITESeq |
| url | https://www.frontiersin.org/articles/10.3389/fcvm.2021.791028/full |
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