Hyporesponsiveness following booster immunization with bacterial polysaccharides is caused by apoptosis of memory B cells.
dc.contributor.author | Brynjolfsson, Siggeir F | |
dc.contributor.author | Henneken, Maren | |
dc.contributor.author | Bjarnarson, Stefania P | |
dc.contributor.author | Mori, Elena | |
dc.contributor.author | Del Giudice, Giuseppe | |
dc.contributor.author | Jonsdottir, Ingileif | |
dc.date.accessioned | 2012-08-14T11:57:53Z | |
dc.date.available | 2012-08-14T11:57:53Z | |
dc.date.issued | 2012-02-01 | |
dc.date.submitted | 2012-08-14 | |
dc.identifier.citation | J. Infect. Dis. 2012, 205(3):422-30 | en_GB |
dc.identifier.issn | 1537-6613 | |
dc.identifier.pmid | 22158565 | |
dc.identifier.doi | 10.1093/infdis/jir750 | |
dc.identifier.uri | http://hdl.handle.net/2336/238397 | |
dc.description | To access publisher full text version of this article. Please click on the hyperlink in Additional Links field. | en_GB |
dc.description.abstract | Repeated 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.sponsorship | University of Iceland, Landspitali University Hospital, | en_GB |
dc.language.iso | en | en |
dc.publisher | Oxford University Press | en_GB |
dc.relation.url | http://dx.doi.org/10.1093/infdis/jir750 | en_GB |
dc.rights | Archived with thanks to The Journal of infectious diseases | en_GB |
dc.subject.mesh | Adjuvants, Immunologic | en_GB |
dc.subject.mesh | Animals | en_GB |
dc.subject.mesh | Animals, Newborn | en_GB |
dc.subject.mesh | Annexin A5 | en_GB |
dc.subject.mesh | Antigens, CD45 | en_GB |
dc.subject.mesh | Apoptosis | en_GB |
dc.subject.mesh | B-Lymphocytes | en_GB |
dc.subject.mesh | Bone Marrow | en_GB |
dc.subject.mesh | Female | en_GB |
dc.subject.mesh | Flow Cytometry | en_GB |
dc.subject.mesh | Immunization, Secondary | en_GB |
dc.subject.mesh | Immunologic Memory | en_GB |
dc.subject.mesh | Immunophenotyping | en_GB |
dc.subject.mesh | Meningococcal Vaccines | en_GB |
dc.subject.mesh | Mice | en_GB |
dc.subject.mesh | Oligodeoxyribonucleotides | en_GB |
dc.subject.mesh | Polysaccharides, Bacterial | en_GB |
dc.subject.mesh | Spleen | en_GB |
dc.subject.mesh | Syndecan-1 | en_GB |
dc.subject.mesh | Vaccines, Conjugate | en_GB |
dc.title | Hyporesponsiveness following booster immunization with bacterial polysaccharides is caused by apoptosis of memory B cells. | en |
dc.type | Article | en |
dc.contributor.department | Department of Immunology, Landspitali, The National University Hospital of Iceland, Reykjavik, Iceland. | en_GB |
dc.identifier.journal | Journal of infectious diseases | en_GB |
dc.rights.access | Landspitali Access - LSH-aðgangur | en |
dc.type.category | Ónæmisfræði | en_GB |
html.description.abstract | Repeated 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. |