title: Natural human antibodies to pneumococcus have distinctive molecular characteristics and protect against pneumococcal disease.
abstract: The molecular and functional characteristics of natural antibody from the preimmune repertoire have not been explored in detail in man. We describe seven human IgM monoclonal antibodies selected on the basis of pneumococcal polysaccharide binding that share both molecular and functional characteristics with natural antibody, suggesting a common B cell lineage origin. Unlike class-switched antibodies, which are serotype-specific, the antibodies were polyreactive and bound all pneumococcal polysaccharide capsular serotypes tested. Some bound endogenous antigens, including blood group antigens and intermediate filament proteins. All the antibodies used unmutated heavy chain V (IGHV) that are expressed at an increased frequency in the elderly and in the preimmune repertoire. The CDR3 was characterized by long length (mean aa 18.4 (+/-4.2) and selective use of IGHD6 (P < 0.001) and IGHJ6 (P < 0.01) family genes. The clones expressing IGHV1-69 and IGHV 3-21 provided significant passive protection against invasive pneumococcal disease in vivo.
authors.affiliation: Infectious Diseases and Microbiology Unit, Institute of Child Health, University College London, London, UK. h.baxendale@ich.ucl.ac.uk
authors.forename: H E
authors.initials: HE
authors.lastname: Baxendale
authors.forename: M
authors.initials: M
authors.lastname: Johnson
authors.forename: R C M
authors.initials: RC
authors.lastname: Stephens
authors.forename: J
authors.initials: J
authors.lastname: Yuste
authors.forename: N
authors.initials: N
authors.lastname: Klein
authors.forename: J S
authors.initials: JS
authors.lastname: Brown
authors.forename: D
authors.initials: D
authors.lastname: Goldblatt
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000235:genetics* / Q000276:immunology*; D000915:Antibody Affinity; D000918:Antibody Specificity; D000937:Antigen-Antibody Reactions; D001324:Autoantigens / Q000276:immunology; D001483:Base Sequence; D016009:Chi-Square Distribution; D003429:Cross Reactions; D005803:Genes, Immunoglobulin; D006801:Humans; D006825:Hybridomas; D007143:Immunoglobulin Heavy Chains; D007075:Immunoglobulin M / Q000276:immunology; D007135:Immunoglobulin Variable Region / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D011008:Pneumococcal Infections / Q000276:immunology*; D022242:Pneumococcal Vaccines / Q000008:administration & dosage*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013296:Streptococcus pneumoniae / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D001324:Autoantigens; D007143:Immunoglobulin Heavy Chains; D007075:Immunoglobulin M; D007135:Immunoglobulin Variable Region; D022242:Pneumococcal Vaccines