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dc.contributor.authorBrynjolfsson, Siggeir F
dc.contributor.authorHenneken, Maren
dc.contributor.authorBjarnarson, Stefania P
dc.contributor.authorMori, Elena
dc.contributor.authorDel Giudice, Giuseppe
dc.contributor.authorJonsdottir, Ingileif
dc.date.accessioned2012-08-14T11:57:53Z
dc.date.available2012-08-14T11:57:53Z
dc.date.issued2012-02-01
dc.date.submitted2012-08-14
dc.identifier.citationJ. Infect. Dis. 2012, 205(3):422-30en_GB
dc.identifier.issn1537-6613
dc.identifier.pmid22158565
dc.identifier.doi10.1093/infdis/jir750
dc.identifier.urihttp://hdl.handle.net/2336/238397
dc.descriptionTo access publisher full text version of this article. Please click on the hyperlink in Additional Links field.en_GB
dc.description.abstractRepeated immunizations with polysaccharide (PS) vaccines cause hyporesponsiveness through undefined mechanisms. We assessed the effects of a PS booster on immune responses, frequency, and survival of PS-specific B-cell subpopulations in spleen and bone marrow. Neonatal mice were primed with meningococcus serotype C (MenC) conjugate MenC-CRM(197)+CpG1826, boosted with MenC-CRM(197), MenC-PS, or saline; subsequently, bromodeoxyuridine (BrdU) was injected daily intraperitoneally. MenC-PS-specific cells were labeled with fluorescent MenC-PS and phenotyped by flow cytometry. After MenC-PS booster, proliferating (BrdU(+)) MenC-PS-specific naive B cells (CD138(-)/B220(+); P = .0003) and plasma cells (CD138(+)/B220(-); P = .0002) in spleen were fewer than after saline booster. BrdU(+) MenC-PS-specific plasma cells were also reduced in bone marrow (P = .0308). Compared to saline, MenC-PS booster reduced BrdU(+) IgG(+) MenC-PS-specific B cells in spleen (P = .0002). Twelve hours after the MenC-PS booster, an increased frequency of apoptotic (AnnexinV(+)) MenC-PS-specific B cells in spleen was observed compared with MenC-CRM(197) (P = .0286) or saline (P = .001) boosters. We demonstrated that the MenC-PS booster significantly reduced the frequency of newly activated MenC-PS-specific B cells-mostly switched IgG(+) memory cells-by driving them into apoptosis. It shows directly that apoptosis of PS-specific memory cells is the cause of PS-induced hyporesponsiveness. These results should be taken into account prior to consideration of the use of PS vaccines.
dc.description.sponsorshipUniversity of Iceland, Landspitali University Hospital,en_GB
dc.language.isoenen
dc.publisherOxford University Pressen_GB
dc.relation.urlhttp://dx.doi.org/10.1093/infdis/jir750en_GB
dc.rightsArchived with thanks to The Journal of infectious diseasesen_GB
dc.subject.meshAdjuvants, Immunologicen_GB
dc.subject.meshAnimalsen_GB
dc.subject.meshAnimals, Newbornen_GB
dc.subject.meshAnnexin A5en_GB
dc.subject.meshAntigens, CD45en_GB
dc.subject.meshApoptosisen_GB
dc.subject.meshB-Lymphocytesen_GB
dc.subject.meshBone Marrowen_GB
dc.subject.meshFemaleen_GB
dc.subject.meshFlow Cytometryen_GB
dc.subject.meshImmunization, Secondaryen_GB
dc.subject.meshImmunologic Memoryen_GB
dc.subject.meshImmunophenotypingen_GB
dc.subject.meshMeningococcal Vaccinesen_GB
dc.subject.meshMiceen_GB
dc.subject.meshOligodeoxyribonucleotidesen_GB
dc.subject.meshPolysaccharides, Bacterialen_GB
dc.subject.meshSpleenen_GB
dc.subject.meshSyndecan-1en_GB
dc.subject.meshVaccines, Conjugateen_GB
dc.titleHyporesponsiveness following booster immunization with bacterial polysaccharides is caused by apoptosis of memory B cells.en
dc.typeArticleen
dc.contributor.departmentDepartment of Immunology, Landspitali, The National University Hospital of Iceland, Reykjavik, Iceland.en_GB
dc.identifier.journalJournal of infectious diseasesen_GB
dc.rights.accessLandspitali Access - LSH-aðganguren
dc.type.categoryÓnæmisfræðien_GB
html.description.abstractRepeated immunizations with polysaccharide (PS) vaccines cause hyporesponsiveness through undefined mechanisms. We assessed the effects of a PS booster on immune responses, frequency, and survival of PS-specific B-cell subpopulations in spleen and bone marrow. Neonatal mice were primed with meningococcus serotype C (MenC) conjugate MenC-CRM(197)+CpG1826, boosted with MenC-CRM(197), MenC-PS, or saline; subsequently, bromodeoxyuridine (BrdU) was injected daily intraperitoneally. MenC-PS-specific cells were labeled with fluorescent MenC-PS and phenotyped by flow cytometry. After MenC-PS booster, proliferating (BrdU(+)) MenC-PS-specific naive B cells (CD138(-)/B220(+); P = .0003) and plasma cells (CD138(+)/B220(-); P = .0002) in spleen were fewer than after saline booster. BrdU(+) MenC-PS-specific plasma cells were also reduced in bone marrow (P = .0308). Compared to saline, MenC-PS booster reduced BrdU(+) IgG(+) MenC-PS-specific B cells in spleen (P = .0002). Twelve hours after the MenC-PS booster, an increased frequency of apoptotic (AnnexinV(+)) MenC-PS-specific B cells in spleen was observed compared with MenC-CRM(197) (P = .0286) or saline (P = .001) boosters. We demonstrated that the MenC-PS booster significantly reduced the frequency of newly activated MenC-PS-specific B cells-mostly switched IgG(+) memory cells-by driving them into apoptosis. It shows directly that apoptosis of PS-specific memory cells is the cause of PS-induced hyporesponsiveness. These results should be taken into account prior to consideration of the use of PS vaccines.


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