title: B-1a and B-1b cells exhibit distinct developmental requirements and have unique functional roles in innate and adaptive immunity to S. pneumoniae.
abstract: B-1a and B-1b lymphocytes were found to exhibit specialized roles in providing immunity to Streptococcus pneumoniae and differ dramatically in their developmental requirements. Transgenic mice overexpressing CD19 (hCD19Tg) generated B-1a cells and natural antibodies that provided protection during infection, while CD19-deficient (CD19(-/-)) mice lacked B-1a cells, lacked natural antibodies, and were more susceptible to infection. By contrast, pneumococcal polysaccharide (PPS) immunization protected CD19(-/-) mice during lethal challenge, whereas hCD19Tg mice remained unprotected. This resulted from differences in the B-1b subset: the key population found to produce protective PPS-specific antibody in both wild-type and CD19(-/-) mice. Thus, CD19(-/-) mice generated B-1b cells and protective adaptive PPS-specific antibody responses, whereas hCD19Tg mice lacked B-1b cells and adaptive PPS-specific antibody responses. This reciprocal contribution of B-1a and B-1b subsets to innate and acquired immunity reveals an unexpected division of labor within the B-1 compartment that is normally balanced by their coordinated development.
authors.affiliation: Department of Immunology, Box 3010, Duke University Medical Center, Durham, North Carolina 27710, USA.
authors.forename: Karen M
authors.initials: KM
authors.lastname: Haas
authors.forename: Jonathan C
authors.initials: JC
authors.lastname: Poe
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Steeber
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Tedder
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000235:genetics / Q000276:immunology*; D018941:Antigens, CD19 / Q000235:genetics*; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D002454:Cell Differentiation; D007113:Immunity, Innate / Q000235:genetics / Q000276:immunology*; D007114:Immunization; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D011008:Pneumococcal Infections / Q000276:immunology* / Q000517:prevention & control; D011135:Polysaccharides, Bacterial / Q000276:immunology*; D013296:Streptococcus pneumoniae / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D018941:Antigens, CD19; D011135:Polysaccharides, Bacterial; C026604:pneumococcal polysaccharide, type III