Pneumococcal polysaccharide abrogates conjugate-induced germinal center reaction and depletes antibody secreting cell pool, causing hyporesponsiveness.
BACKGROUND
Plain pneumococcal polysaccharide (PPS) booster administered during second year of life has been shown to cause hyporesponsiveness. We assessed the effects of PPS booster on splenic memory B cell responses and persistence of PPS-specific long-lived plasma cells in the bone marrow (BM).


METHODS
Neonatal mice were primed subcutanously (s.c.) or intranasally (i.n.) with pneumococcal conjugate (Pnc1-TT) and the adjuvant LT-K63, and boosted with PPS+LT-K63 or saline 1, 2 or 3 times with 16 day intervals. Seven days after each booster, spleens were removed, germinal centers (GC), IgM(+), IgG(+) follicles and PPS-specific antibody secreting cells (AbSC) in spleen and BM enumerated.


RESULTS
PPS booster s.c., but not i.n., compromised the Pnc1-TT-induced PPS-specific Abs by abrogating the Pnc1-TT-induced GC reaction and depleting PPS-specific AbSCs in spleen and limiting their homing to the BM. There was no difference in the frequency of PPS-specific AbSCs in spleen and BM between mice that received 1, 2 or 3 PPS boosters s.c.. Repeated PPS+LT-K63 booster i.n. reduced the frequency of PPS-specific IgG(+) AbSCs in BM.


CONCLUSIONS
PPS booster-induced hyporesponsiveness is caused by abrogation of conjugate-induced GC reaction and depletion of PPS-specific IgG(+) AbSCs resulting in no homing of new PPS-specific long-lived plasma cells to the BM or survival. These results should be taken into account in design of vaccination schedules where polysaccharides are being considered.
Landspitali, The National University Hospital of Iceland, Department of Immunology, Reykjavik, Iceland ; University of Iceland, Faculty of Medicine, Reykjavik, Iceland.
Stefania P
SP
Bjarnarson
Hreinn
H
Benonisson
Giuseppe
G
Del Giudice
Ingileif
I
Jonsdottir
D000818:Animals; D000921:Antibody-Producing Cells / Q000276:immunology*; D001853:Bone Marrow / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D018858:Germinal Center / Q000276:immunology*; D007150:Immunohistochemistry; D051379:Mice; D022242:Pneumococcal Vaccines / Q000276:immunology*; D013154:Spleen / Q000378:metabolism; D013296:Streptococcus pneumoniae / Q000276:immunology*
D022242:Pneumococcal Vaccines