The Differential Complement, Fc and Chemokine Receptor Expression of B Cells in IgG4-Related Pancreatobiliary Disease and Primary Sclerosing Cholangitis and Its Relevance for Targeting B Cell Pathways in Disease
<b>Background:</b> Immune-mediated liver and biliary conditions, such as IgG4-related pancreatobiliary disease (IgG4-PB) and a subset of primary sclerosing cholangitis (PSC- high(h)IgG4), exhibit increased IgG4 levels in the blood. The relative expression of IgG4+ and IgG1+ B cells in th...
Saved in:
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2024-12-01
|
| Series: | Biomedicines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2227-9059/12/12/2839 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1846105613247971328 |
|---|---|
| author | Tamsin Cargill Eleanor Barnes Theo Rispens Emma L. Culver |
| author_facet | Tamsin Cargill Eleanor Barnes Theo Rispens Emma L. Culver |
| author_sort | Tamsin Cargill |
| collection | DOAJ |
| description | <b>Background:</b> Immune-mediated liver and biliary conditions, such as IgG4-related pancreatobiliary disease (IgG4-PB) and a subset of primary sclerosing cholangitis (PSC- high(h)IgG4), exhibit increased IgG4 levels in the blood. The relative expression of IgG4+ and IgG1+ B cells in the blood and the expression of complement and Fc receptors on these IgG1+ and IgG4+ B cells in IgG4-PB and PSC have not been previously described. We hypothesised that the patterns of expression of these cells and their receptors would differ, are relevant to disease pathogenesis and may represent therapeutic targets. <b>Methods:</b> CD19+ B cells were sorted from blood collected from patients with IgG4-PB, PSC-high(h)IgG4 and healthy volunteers. Cells were stained with fluorescent labelled antibodies specific to IgG1, IgG4, complement receptors (CR1 and CR2), Fc receptors (FcεRII and FcγRIIb) and chemokine receptors (CXCR3, CXCR4, CXCR5) and were analysed by flow cytometry. <b>Findings:</b> IgG4-PB, compared to healthy volunteers, showed decreased CR2 expression on IgG1+ B cells (MFI 416 (275–552) vs. 865 (515–3631), <i>p</i> = 0.04) and IgG4+ B cells (MFI 337 (231–353) vs. 571 (398–2521), <i>p</i> = 0.03). IgG4-PB, compared to healthy volunteers, showed increased FcεRII expression on IgG4+ B cells (MFI 296 (225–617) vs. 100 (92–138), <i>p</i> = 0.0145) and decreased FcγRIIb expression on IgG1+ B cells (134 (72–161) vs. 234 (175–291), <i>p</i> = 0.0262). FcγRIIb expression was also decreased in IgG1+ B cells in patients with PSC-hIgG4 compared to healthy volunteers. <b>Conclusions:</b> This exploratory study indicates that in IgG4-PB, B cells have decreased CR2 and FcγRIIb expression and increased FcεRII expression, suggesting altered sensitivity to complement, IgG-mediated inhibition and sensitisation by IgE, which may promote the relative expansion of IgG4+ B cells in this disease. |
| format | Article |
| id | doaj-art-0bd8baf0ab3c4ed982f3ffdcfa8f9a4d |
| institution | Kabale University |
| issn | 2227-9059 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj-art-0bd8baf0ab3c4ed982f3ffdcfa8f9a4d2024-12-27T14:13:01ZengMDPI AGBiomedicines2227-90592024-12-011212283910.3390/biomedicines12122839The Differential Complement, Fc and Chemokine Receptor Expression of B Cells in IgG4-Related Pancreatobiliary Disease and Primary Sclerosing Cholangitis and Its Relevance for Targeting B Cell Pathways in DiseaseTamsin Cargill0Eleanor Barnes1Theo Rispens2Emma L. Culver3Peter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford, South Parks Road, Oxford OX1 3SY, UKPeter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford, South Parks Road, Oxford OX1 3SY, UKSanquin, Division Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Plesmanlaan 125, 1066 CX Amsterdam, The NetherlandsPeter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford, South Parks Road, Oxford OX1 3SY, UK<b>Background:</b> Immune-mediated liver and biliary conditions, such as IgG4-related pancreatobiliary disease (IgG4-PB) and a subset of primary sclerosing cholangitis (PSC- high(h)IgG4), exhibit increased IgG4 levels in the blood. The relative expression of IgG4+ and IgG1+ B cells in the blood and the expression of complement and Fc receptors on these IgG1+ and IgG4+ B cells in IgG4-PB and PSC have not been previously described. We hypothesised that the patterns of expression of these cells and their receptors would differ, are relevant to disease pathogenesis and may represent therapeutic targets. <b>Methods:</b> CD19+ B cells were sorted from blood collected from patients with IgG4-PB, PSC-high(h)IgG4 and healthy volunteers. Cells were stained with fluorescent labelled antibodies specific to IgG1, IgG4, complement receptors (CR1 and CR2), Fc receptors (FcεRII and FcγRIIb) and chemokine receptors (CXCR3, CXCR4, CXCR5) and were analysed by flow cytometry. <b>Findings:</b> IgG4-PB, compared to healthy volunteers, showed decreased CR2 expression on IgG1+ B cells (MFI 416 (275–552) vs. 865 (515–3631), <i>p</i> = 0.04) and IgG4+ B cells (MFI 337 (231–353) vs. 571 (398–2521), <i>p</i> = 0.03). IgG4-PB, compared to healthy volunteers, showed increased FcεRII expression on IgG4+ B cells (MFI 296 (225–617) vs. 100 (92–138), <i>p</i> = 0.0145) and decreased FcγRIIb expression on IgG1+ B cells (134 (72–161) vs. 234 (175–291), <i>p</i> = 0.0262). FcγRIIb expression was also decreased in IgG1+ B cells in patients with PSC-hIgG4 compared to healthy volunteers. <b>Conclusions:</b> This exploratory study indicates that in IgG4-PB, B cells have decreased CR2 and FcγRIIb expression and increased FcεRII expression, suggesting altered sensitivity to complement, IgG-mediated inhibition and sensitisation by IgE, which may promote the relative expansion of IgG4+ B cells in this disease.https://www.mdpi.com/2227-9059/12/12/2839IgG4IgG4-related diseaseprimary sclerosing cholangitisB cellsFc receptorcomplement |
| spellingShingle | Tamsin Cargill Eleanor Barnes Theo Rispens Emma L. Culver The Differential Complement, Fc and Chemokine Receptor Expression of B Cells in IgG4-Related Pancreatobiliary Disease and Primary Sclerosing Cholangitis and Its Relevance for Targeting B Cell Pathways in Disease Biomedicines IgG4 IgG4-related disease primary sclerosing cholangitis B cells Fc receptor complement |
| title | The Differential Complement, Fc and Chemokine Receptor Expression of B Cells in IgG4-Related Pancreatobiliary Disease and Primary Sclerosing Cholangitis and Its Relevance for Targeting B Cell Pathways in Disease |
| title_full | The Differential Complement, Fc and Chemokine Receptor Expression of B Cells in IgG4-Related Pancreatobiliary Disease and Primary Sclerosing Cholangitis and Its Relevance for Targeting B Cell Pathways in Disease |
| title_fullStr | The Differential Complement, Fc and Chemokine Receptor Expression of B Cells in IgG4-Related Pancreatobiliary Disease and Primary Sclerosing Cholangitis and Its Relevance for Targeting B Cell Pathways in Disease |
| title_full_unstemmed | The Differential Complement, Fc and Chemokine Receptor Expression of B Cells in IgG4-Related Pancreatobiliary Disease and Primary Sclerosing Cholangitis and Its Relevance for Targeting B Cell Pathways in Disease |
| title_short | The Differential Complement, Fc and Chemokine Receptor Expression of B Cells in IgG4-Related Pancreatobiliary Disease and Primary Sclerosing Cholangitis and Its Relevance for Targeting B Cell Pathways in Disease |
| title_sort | differential complement fc and chemokine receptor expression of b cells in igg4 related pancreatobiliary disease and primary sclerosing cholangitis and its relevance for targeting b cell pathways in disease |
| topic | IgG4 IgG4-related disease primary sclerosing cholangitis B cells Fc receptor complement |
| url | https://www.mdpi.com/2227-9059/12/12/2839 |
| work_keys_str_mv | AT tamsincargill thedifferentialcomplementfcandchemokinereceptorexpressionofbcellsinigg4relatedpancreatobiliarydiseaseandprimarysclerosingcholangitisanditsrelevancefortargetingbcellpathwaysindisease AT eleanorbarnes thedifferentialcomplementfcandchemokinereceptorexpressionofbcellsinigg4relatedpancreatobiliarydiseaseandprimarysclerosingcholangitisanditsrelevancefortargetingbcellpathwaysindisease AT theorispens thedifferentialcomplementfcandchemokinereceptorexpressionofbcellsinigg4relatedpancreatobiliarydiseaseandprimarysclerosingcholangitisanditsrelevancefortargetingbcellpathwaysindisease AT emmalculver thedifferentialcomplementfcandchemokinereceptorexpressionofbcellsinigg4relatedpancreatobiliarydiseaseandprimarysclerosingcholangitisanditsrelevancefortargetingbcellpathwaysindisease AT tamsincargill differentialcomplementfcandchemokinereceptorexpressionofbcellsinigg4relatedpancreatobiliarydiseaseandprimarysclerosingcholangitisanditsrelevancefortargetingbcellpathwaysindisease AT eleanorbarnes differentialcomplementfcandchemokinereceptorexpressionofbcellsinigg4relatedpancreatobiliarydiseaseandprimarysclerosingcholangitisanditsrelevancefortargetingbcellpathwaysindisease AT theorispens differentialcomplementfcandchemokinereceptorexpressionofbcellsinigg4relatedpancreatobiliarydiseaseandprimarysclerosingcholangitisanditsrelevancefortargetingbcellpathwaysindisease AT emmalculver differentialcomplementfcandchemokinereceptorexpressionofbcellsinigg4relatedpancreatobiliarydiseaseandprimarysclerosingcholangitisanditsrelevancefortargetingbcellpathwaysindisease |