title: Induction of in vivo antipolysaccharide immunoglobulin responses to intact Streptococcus pneumoniae is more heavily dependent on Btk-mediated B-cell receptor signaling than antiprotein responses.
abstract: The relative role of Btk-dependent B-cell receptor (BCR) signaling in the induction of antipolysaccharide (anti-PS) and antiprotein immunoglobulin (Ig) responses to an intact extracellular bacterium in vivo is unknown. Btklow mice exhibit reduced BCR signaling but largely restore B-cell development. Btklow mice immunized with intact Streptococcus pneumoniae elicit reduced anti-PS but normal antiprotein Ig responses. Immunization of Btklow mice with PS-protein conjugate in saline results in an even more profound defect in the anti-PS but not antiprotein response, which is largely restored by use of a CpG-containing oligodeoxynucleotide as an adjuvant. These data demonstrate a greater dependence on Btk-mediated BCR signaling for physiologic anti-PS relative to antiprotein responses, as well as the existence of a compensatory Toll-like-receptor-mediated signaling pathway naturally triggered in response to intact bacterial pathogens.
authors.affiliation: Department of Pathology, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814-4799, USA.
authors.forename: Abdul Q
authors.initials: AQ
authors.lastname: Khan
authors.forename: Goutam
authors.initials: G
authors.lastname: Sen
authors.forename: Shuling
authors.initials: S
authors.lastname: Guo
authors.forename: Owen N
authors.initials: ON
authors.lastname: Witte
authors.forename: Clifford M
authors.initials: CM
authors.lastname: Snapper
mesh_terms: D000077329:Agammaglobulinaemia Tyrosine Kinase; D000818:Animals; D001426:Bacterial Proteins / Q000276:immunology*; D007136:Immunoglobulins / Q000097:blood*; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D010537:Peritoneum / Q000166:cytology / Q000276:immunology; D011135:Polysaccharides, Bacterial / Q000276:immunology*; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism; D015398:Signal Transduction; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013296:Streptococcus pneumoniae / Q000276:immunology*
chemical_list: D001426:Bacterial Proteins; D007136:Immunoglobulins; D011135:Polysaccharides, Bacterial; D011947:Receptors, Antigen, B-Cell; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase