Suppressive effect of bacterial polysaccharides on BAFF system is responsible for their poor immunogenicity.
Capsular polysaccharides of encapsulated bacteria are weakly immunogenic T cell-independent type 2 (TI-2) Ags. Recent findings suggest that BAFF system molecules have a critical role in the development of Ab responses against TI-2 Ags. In this study, we investigated the effect of bacterial polysaccharides on B cell responses to BAFF and a proliferation-inducing ligand (APRIL). We determined that B cells exposed to meningococcal type C polysaccharide (MCPS) or group B Streptococcus serotype V (GBS-V) were unresponsive to BAFF- and APRIL-induced Ig secretion. Moreover, MCPS and GBS-V strongly downregulated transmembrane activator and calcium-modulator and cyclophilin ligand interactor, the BAFF and APRIL receptor that is responsible for Ab development against TI-2 Ags. Interestingly, (4-hydroxy-3-nitrophenyl)acetyl-Ficoll (NP-Ficoll), a prototype TI-2 Ag, did not manifest a suppressive effect on B cells. Paradoxically, whereas GBS-V and MCPS inhibited IFN-γ-induced BAFF production from dendritic cells, NP-Ficoll strongly increased BAFF secretion. TLR 9 agonist CpG deoxyoligonucleotide (ODN) was able to reverse the MCPS-mediated transmembrane activator and calcium-modulator and cyclophilin ligand interactor suppression but could not rescue the Ig secretion in BAFF- or APRIL-stimulated B cells. In support of these in vitro observations, it was observed that CpG ODN could help augment the Ab response against NP in mice immunized with a CpG ODN-containing NP-Ficoll vaccine but exhibited only marginal adjuvant activity for MCPS vaccine. Collectively, these results suggest a mechanism for the weak immunogenicity of bacterial polysaccharides and explain the previously observed differences between bacterial polysaccharide and NP-Ficoll immunogenicity.
Laboratory of Bacterial Polysaccharides, Division of Bacterial Parasitic and Allergenic Products, Center for Biologics Evaluation and Research, US Food and Drug Administration, Bethesda, MD 20852, USA.
Sunita
S
Kanswal
Nora
N
Katsenelson
Windy
W
Allman
Kadriye
K
Uslu
Milan S
MS
Blake
Mustafa
M
Akkoyunlu
D000818:Animals; D053264:B-Cell Activating Factor / Q000037:antagonists & inhibitors* / Q000502:physiology*; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016667:Bacterial Capsules / Q000494:pharmacology*; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000276:immunology; D002478:Cells, Cultured; D004306:Dose-Response Relationship, Immunologic; D006131:Growth Inhibitors / Q000037:antagonists & inhibitors / Q000502:physiology; D007166:Immunosuppressive Agents / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000502:physiology; D038542:Neisseria meningitidis, Serogroup C / Q000276:immunology*; D011135:Polysaccharides, Bacterial / Q000494:pharmacology / Q000502:physiology*; D015398:Signal Transduction / Q000276:immunology
D053264:B-Cell Activating Factor; D001428:Bacterial Vaccines; D006131:Growth Inhibitors; D007166:Immunosuppressive Agents; D016328:NF-kappa B; D011135:Polysaccharides, Bacterial; C505720:Tnfsf13b protein, mouse; C068312:capsular polysaccharide, streptoccal group B type V