{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T20:29:50Z","timestamp":1786480190135,"version":"build-2736575974"},"reference-count":41,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","license":[{"start":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T00:00:00Z","timestamp":1769472000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Kidney360"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:sec>\n                    <jats:title>Key Points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Tolerant patients of kidney graft exhibit higher IgA production than other kidney transplanted patients without modification for IgG.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>IgA-expressing B cells from tolerant patients expressed granzyme B and exert regulatory functions through granzyme B production.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Tolerant kidney transplant recipients without immunosuppression have a high frequency of circulating granzyme B (GZMB)\u2013expressing regulatory B cells (Breg). Because the precursors of these Bregs remain unknown and IgA-secreting B cells have been shown to have regulatory properties in different situations, we investigated the association between IgA- and GZMB-expressing B cells in a case-control study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Forty-five healthy volunteers and 31 kidney transplant recipients with either stable graft function under immunosuppression (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      =10), antibody-mediated rejection (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      =7), or tolerant patients (TOL;\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      =14) were included. Serum immunoglobulin concentrations as glycosylation were measured by ELISA; forms of IgA were examined by Western blot. Bregs were analyzed by single-cell RNA sequencing and multiparameter spectral flow cytometry. Their function was assessed in cocultured with\n                      <jats:italic toggle=\"yes\">T<\/jats:italic>\n                      cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Serum IgA concentration was elevated in TOL compared with other transplanted patients, especially the noninflammatory IgA1 subclass, without changes in IgA size or glycosylation. Single-cell transcriptomic analysis revealed higher IgA gene expression in GZMB expressing B cells and conversely higher GZMB gene expression in IgA-expressing B cells. Phenotyping analysis by spectral multiparameter flow cytometry showed that IgA+ B cells were memory B cells, and that IgA+ B cells from TOL tended to express more GZMB compared with antibody-mediated rejection patients. In functional assays, IgA+ B cells exhibited high regulatory functions that were partially prevented by the presence of GZMB inhibitor.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These data show a strong association between IgA+ and GZMB+ Bregs, particularly in tolerant kidney transplant recipients with higher GZMB and IgA expression and greater suppressive properties.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Trial registry name and registration number:<\/jats:title>\n                    <jats:p>NCT02900040.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.34067\/kid.0000001054","type":"journal-article","created":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T17:00:43Z","timestamp":1769533243000},"page":"1251-1261","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":0,"title":["IgA-Producing B Cells Exert Regulatory Function through Granzyme B in Kidney Allograft Tolerance"],"prefix":"10.34067","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9306-9247","authenticated-orcid":false,"given":"Laureline","family":"Berthelot","sequence":"first","affiliation":[{"name":"Inserm, Nantes Universit\u00e9, CHU de Nantes, Center for Research in Transplantation and Translational Immunology CR2TI, UMR 1064, ITUN, Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2990-3513","authenticated-orcid":false,"given":"Nicolas","family":"Degauque","sequence":"additional","affiliation":[{"name":"Inserm, Nantes Universit\u00e9, CHU de Nantes, Center for Research in Transplantation and Translational Immunology CR2TI, UMR 1064, ITUN, Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Cappelier","sequence":"additional","affiliation":[{"name":"Inserm, Nantes Universit\u00e9, CHU de Nantes, Center for Research in Transplantation and Translational Immunology CR2TI, UMR 1064, ITUN, Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0232-1663","authenticated-orcid":false,"given":"Nicolas","family":"Sailliet","sequence":"additional","affiliation":[{"name":"Inserm, Nantes Universit\u00e9, CHU de Nantes, Center for Research in Transplantation and Translational Immunology CR2TI, UMR 1064, ITUN, Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5432-6741","authenticated-orcid":false,"given":"Camille","family":"Math\u00e9","sequence":"additional","affiliation":[{"name":"Inserm, Nantes Universit\u00e9, CHU de Nantes, Center for Research in Transplantation and Translational Immunology CR2TI, UMR 1064, ITUN, Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7ois","family":"Brinas","sequence":"additional","affiliation":[{"name":"Inserm, Nantes Universit\u00e9, CHU de Nantes, Center for Research in Transplantation and Translational Immunology CR2TI, UMR 1064, ITUN, Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amandine","family":"Dupuy","sequence":"additional","affiliation":[{"name":"Inserm, Nantes Universit\u00e9, CHU de Nantes, Center for Research in Transplantation and Translational Immunology CR2TI, UMR 1064, ITUN, Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8437-666X","authenticated-orcid":false,"given":"L\u00e9o","family":"Boussamet","sequence":"additional","affiliation":[{"name":"Inserm, Nantes Universit\u00e9, CHU de Nantes, Center for Research in Transplantation and Translational Immunology CR2TI, UMR 1064, ITUN, Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaelle","family":"Tilly","sequence":"additional","affiliation":[{"name":"Inserm, Nantes Universit\u00e9, CHU de Nantes, Center for Research in Transplantation and Translational Immunology CR2TI, UMR 1064, ITUN, Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8226-4250","authenticated-orcid":false,"given":"Luc","family":"Colas","sequence":"additional","affiliation":[{"name":"Inserm, Nantes Universit\u00e9, CHU de Nantes, Center for Research in Transplantation and 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France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7641-1592","authenticated-orcid":false,"given":"Magali","family":"Giral","sequence":"additional","affiliation":[{"name":"Inserm, Nantes Universit\u00e9, CHU de Nantes, Center for Research in Transplantation and Translational Immunology CR2TI, UMR 1064, ITUN, Nantes, France"},{"name":"Department of Nephrology, CHU de Nantes, Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5058-795X","authenticated-orcid":false,"given":"Richard","family":"Danger","sequence":"additional","affiliation":[{"name":"Inserm, Nantes Universit\u00e9, CHU de Nantes, Center for Research in Transplantation and Translational Immunology CR2TI, UMR 1064, ITUN, Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2099-4420","authenticated-orcid":false,"given":"Hoa 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