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Siggeir F. Brynjolfsson, Maren Henneken, Stefania P. Bjarnarson, Elena Mori, Giuseppe Del Giudice, Ingileif Jonsdottir, Hyporesponsiveness Following Booster Immunization With Bacterial Polysaccharides Is Caused by Apoptosis of Memory B Cells, The Journal of Infectious Diseases, Volume 205, Issue 3, 1 February 2012, Pages 422–430, https://doi.org/10.1093/infdis/jir750
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Abstract
Background. 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.
Methods. Neonatal mice were primed with meningococcus serotype C (MenC) conjugate MenC-CRM197+CpG1826, boosted with MenC-CRM197, 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.
Results. 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-CRM197 (P = .0286) or saline (P = .001) boosters.
Conclusions. 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.
