{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T13:54:08Z","timestamp":1791294848519,"version":"4.1.0"},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2012,4,1]],"date-time":"2012-04-01T00:00:00Z","timestamp":1333238400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>B cells require MHC class II (MHC II)-restricted cognate help and CD40 engagement by CD4+ T follicular helper (TFH) cells to form germinal centers and long-lasting Ab responses. Invariant NKT (iNKT) cells are innate-like lymphocytes that jumpstart the adaptive immune response when activated by the CD1d-restricted lipid \u03b1-galactosylceramide (\u03b1GalCer). We previously observed that immunization of mice lacking CD4+ T cells (MHC II\u2212\/\u2212) elicits specific IgG responses only when protein Ags are mixed with \u03b1GalCer. In this study, we investigated the mechanisms underpinning this observation. We find that induction of Ag-specific Ab responses in MHC II\u2212\/\u2212 mice upon immunization with protein Ags mixed with \u03b1GalCer requires CD1d expression and CD40 engagement on B cells, suggesting that iNKT cells provide CD1d-restricted cognate help for B cells. Remarkably, splenic iNKT cells from immunized MHC II\u2212\/\u2212 mice display a typical CXCR5hiprogrammed death-1hiICOShiBcl-6hi TFH phenotype and induce germinal centers. The specific IgG response induced in MHC II\u2212\/\u2212 mice has shorter duration than that developing in CD4-competent animals, suggesting that iNKTFH cells preferentially induce transient rather than long-lived Ab responses. Together, these results suggest that iNKT cells can be co-opted into the follicular helper function, yet iNKTFH and CD4+ TFH cells display distinct helper features, consistent with the notion that these two cell subsets play nonredundant functions throughout immune responses.<\/jats:p>","DOI":"10.4049\/jimmunol.1103501","type":"journal-article","created":{"date-parts":[[2012,3,1]],"date-time":"2012-03-01T06:30:57Z","timestamp":1330583457000},"page":"3217-3222","source":"Crossref","is-referenced-by-count":106,"title":["Follicular Helper NKT Cells Induce Limited B Cell Responses and Germinal Center Formation in the Absence of CD4+ T Cell Help"],"prefix":"10.1093","volume":"188","author":[{"given":"Elena","family":"Tonti","sequence":"first","affiliation":[{"name":"Experimental Immunology Unit, Division of Immunology, Transplantation and Infectious Diseases, San Raffaele Scientific Institute , 20132 Milan ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maya","family":"Fedeli","sequence":"additional","affiliation":[{"name":"Experimental Immunology Unit, Division of Immunology, Transplantation and Infectious Diseases, San Raffaele Scientific Institute , 20132 Milan ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Napolitano","sequence":"additional","affiliation":[{"name":"Experimental Immunology Unit, Division of Immunology, Transplantation and Infectious Diseases, San Raffaele Scientific Institute , 20132 Milan ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Iannacone","sequence":"additional","affiliation":[{"name":"Dynamics of Immune Responses Unit, Division of Immunology, Transplantation and Infectious Diseases, San Raffaele Scientific Institute , 20132 Milan ,","place":["Italy"]},{"name":"Division of Immunology, Immune Disease Institute, Harvard Medical School , Boston, MA 02115"},{"name":"Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School , Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrich H","family":"von Andrian","sequence":"additional","affiliation":[{"name":"Division of Immunology, Immune Disease Institute, Harvard Medical School , Boston, MA 02115"},{"name":"Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School , Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca G","family":"Guidotti","sequence":"additional","affiliation":[{"name":"Immunopathogenesis of Liver Infections Unit, Division of Immunology, Transplantation and Infectious Diseases, San Raffaele Scientific Institute , 20132 Milan ,","place":["Italy"]},{"name":"Department of Immunology and Microbial Sciences, The Scripps Research Institute , La Jolla, CA 92037"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"Abrignani","sequence":"additional","affiliation":[{"name":"Istituto Nazionale Genetica Molecolare , 20122 Milan ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Casorati","sequence":"additional","affiliation":[{"name":"Experimental Immunology Unit, Division of Immunology, Transplantation and Infectious Diseases, San Raffaele Scientific Institute , 20132 Milan ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Dellabona","sequence":"additional","affiliation":[{"name":"Experimental Immunology Unit, Division of Immunology, Transplantation and Infectious Diseases, San Raffaele Scientific Institute , 20132 Milan ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2012,4,1]]},"reference":[{"key":"2025032410002417200_r1","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1146\/annurev.iy.12.040194.001001","article-title":"Germinal centers","volume":"12","author":"MacLennan","year":"1994","journal-title":"Annu. 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