Activation-induced cytidine deaminase expression by thymic B cells promotes T-cell tolerance and limits autoimmunity
Summary: Elimination of self-reactive T cells in the thymus is critical to establish T-cell tolerance. A growing body of evidence suggests a role for thymic B cells in the elimination of self-reactive thymocytes. To specifically address the role of thymic B cells in central tolerance, we investigate...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2023-01-01
|
| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004222021253 |
| _version_ | 1797946175195709440 |
|---|---|
| author | Félix Lombard-Vadnais Geneviève Chabot-Roy Astrid Zahn Sahily Rodriguez Torres Javier M. Di Noia Heather J. Melichar Sylvie Lesage |
| author_facet | Félix Lombard-Vadnais Geneviève Chabot-Roy Astrid Zahn Sahily Rodriguez Torres Javier M. Di Noia Heather J. Melichar Sylvie Lesage |
| author_sort | Félix Lombard-Vadnais |
| collection | DOAJ |
| description | Summary: Elimination of self-reactive T cells in the thymus is critical to establish T-cell tolerance. A growing body of evidence suggests a role for thymic B cells in the elimination of self-reactive thymocytes. To specifically address the role of thymic B cells in central tolerance, we investigated the phenotype of thymic B cells in various mouse strains, including non-obese diabetic (NOD) mice, a model of autoimmune diabetes. We noted that isotype switching of NOD thymic B cells is reduced as compared to other, autoimmune-resistant, mouse strains. To determine the impact of B cell isotype switching on thymocyte selection and tolerance, we generated NOD.AID−/− mice. Diabetes incidence was enhanced in these mice. Moreover, we observed reduced clonal deletion and a resulting increase in self-reactive CD4+ T cells in NOD.AID−/− mice relative to NOD controls. Together, this study reveals that AID expression in thymic B cells contributes to T-cell tolerance. |
| first_indexed | 2024-04-10T21:06:43Z |
| format | Article |
| id | doaj.art-9b81a4e25aaf4411bb07d99e56fa8083 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-04-10T21:06:43Z |
| publishDate | 2023-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-9b81a4e25aaf4411bb07d99e56fa80832023-01-22T04:41:28ZengElsevieriScience2589-00422023-01-01261105852Activation-induced cytidine deaminase expression by thymic B cells promotes T-cell tolerance and limits autoimmunityFélix Lombard-Vadnais0Geneviève Chabot-Roy1Astrid Zahn2Sahily Rodriguez Torres3Javier M. Di Noia4Heather J. Melichar5Sylvie Lesage6Immunologie-oncologie, Centre de recherche de l’Hôpital Maisonneuve-Rosemont, Montréal, QC H1T 2M4, Canada; Department of Microbiology & Immunology, McGill University, Montreal, QC H3A 0G4, CanadaImmunologie-oncologie, Centre de recherche de l’Hôpital Maisonneuve-Rosemont, Montréal, QC H1T 2M4, CanadaUnité de recherche en biologie moléculaire des cellules B, Institut de recherches cliniques de Montréal, Montréal, QC H2W 1R7, CanadaImmunologie-oncologie, Centre de recherche de l’Hôpital Maisonneuve-Rosemont, Montréal, QC H1T 2M4, Canada; Département de microbiologie, infectiologie et immunologie, Université de Montréal, Montréal, QC H3T 1J4, CanadaDepartment of Microbiology & Immunology, McGill University, Montreal, QC H3A 0G4, Canada; Unité de recherche en biologie moléculaire des cellules B, Institut de recherches cliniques de Montréal, Montréal, QC H2W 1R7, Canada; Département de médecine, Université de Montréal, Montréal, QC H3T 1J4, Canada; Department of Experimental Medicine, McGill University, Montreal, QC H3A 0G4, CanadaImmunologie-oncologie, Centre de recherche de l’Hôpital Maisonneuve-Rosemont, Montréal, QC H1T 2M4, Canada; Département de médecine, Université de Montréal, Montréal, QC H3T 1J4, Canada; Corresponding authorImmunologie-oncologie, Centre de recherche de l’Hôpital Maisonneuve-Rosemont, Montréal, QC H1T 2M4, Canada; Département de microbiologie, infectiologie et immunologie, Université de Montréal, Montréal, QC H3T 1J4, Canada; Corresponding authorSummary: Elimination of self-reactive T cells in the thymus is critical to establish T-cell tolerance. A growing body of evidence suggests a role for thymic B cells in the elimination of self-reactive thymocytes. To specifically address the role of thymic B cells in central tolerance, we investigated the phenotype of thymic B cells in various mouse strains, including non-obese diabetic (NOD) mice, a model of autoimmune diabetes. We noted that isotype switching of NOD thymic B cells is reduced as compared to other, autoimmune-resistant, mouse strains. To determine the impact of B cell isotype switching on thymocyte selection and tolerance, we generated NOD.AID−/− mice. Diabetes incidence was enhanced in these mice. Moreover, we observed reduced clonal deletion and a resulting increase in self-reactive CD4+ T cells in NOD.AID−/− mice relative to NOD controls. Together, this study reveals that AID expression in thymic B cells contributes to T-cell tolerance.http://www.sciencedirect.com/science/article/pii/S2589004222021253ImmunologyImmunity |
| spellingShingle | Félix Lombard-Vadnais Geneviève Chabot-Roy Astrid Zahn Sahily Rodriguez Torres Javier M. Di Noia Heather J. Melichar Sylvie Lesage Activation-induced cytidine deaminase expression by thymic B cells promotes T-cell tolerance and limits autoimmunity iScience Immunology Immunity |
| title | Activation-induced cytidine deaminase expression by thymic B cells promotes T-cell tolerance and limits autoimmunity |
| title_full | Activation-induced cytidine deaminase expression by thymic B cells promotes T-cell tolerance and limits autoimmunity |
| title_fullStr | Activation-induced cytidine deaminase expression by thymic B cells promotes T-cell tolerance and limits autoimmunity |
| title_full_unstemmed | Activation-induced cytidine deaminase expression by thymic B cells promotes T-cell tolerance and limits autoimmunity |
| title_short | Activation-induced cytidine deaminase expression by thymic B cells promotes T-cell tolerance and limits autoimmunity |
| title_sort | activation induced cytidine deaminase expression by thymic b cells promotes t cell tolerance and limits autoimmunity |
| topic | Immunology Immunity |
| url | http://www.sciencedirect.com/science/article/pii/S2589004222021253 |
| work_keys_str_mv | AT felixlombardvadnais activationinducedcytidinedeaminaseexpressionbythymicbcellspromotestcelltoleranceandlimitsautoimmunity AT genevievechabotroy activationinducedcytidinedeaminaseexpressionbythymicbcellspromotestcelltoleranceandlimitsautoimmunity AT astridzahn activationinducedcytidinedeaminaseexpressionbythymicbcellspromotestcelltoleranceandlimitsautoimmunity AT sahilyrodrigueztorres activationinducedcytidinedeaminaseexpressionbythymicbcellspromotestcelltoleranceandlimitsautoimmunity AT javiermdinoia activationinducedcytidinedeaminaseexpressionbythymicbcellspromotestcelltoleranceandlimitsautoimmunity AT heatherjmelichar activationinducedcytidinedeaminaseexpressionbythymicbcellspromotestcelltoleranceandlimitsautoimmunity AT sylvielesage activationinducedcytidinedeaminaseexpressionbythymicbcellspromotestcelltoleranceandlimitsautoimmunity |