title: Intact antiinfluenza virus immune response in targeted kappa-deficient mice.
abstract: Immunoglobulins are encoded by genes located in three different loci, the heavy chain (IgH), kappa light chain (Ig kappa), and lambda light chain (Ig lambda) loci. In mice, the kappa/lambda ratio of B cells is 95:5. In a previous study, we reported that kappa gene deletion causes the alternative usage of lambda 1 (93%) and lambda 2 (7%) light chains, and that the kappa anti-TNP repertoire is compensated for by the lambda repertoire even though the latter is clonally restricted in K-/- mice. To investigate the contribution of lambda antibodies to protection against virus, we compared K-/- mice with 129/Sv wild-type mice with respect to immune responses to influenza virus. PR8 virus immunized K-/- and 129/Sv mice showed no difference in the titer of anti-HA antibodies. Furthermore, the same immunized mice had sufficiently high neutralizing antibody titer to prevent infection when challenged with 7.5 x 10(4) TCID50 of PR8 virus. In addition, immunized K-/- mice were resistant to infection with 7.5 x 10(4) TCID50 and 7.5 x 10(5) TCID50 (10 and 100 LD50, respectively) of PR8 virus. Finally, K-/- mice are also capable of inducing cytotoxic T cells. These results suggest that the lambda repertoire can compensate for the kappa repertoire by generating a fully protective neutralizing antibody response.
authors.affiliation: Mount Sinai School of Medicine, New York, New York.
authors.forename: H
authors.initials: H
authors.lastname: Isobe
authors.forename: F
authors.initials: F
authors.lastname: Alt
authors.forename: C A
authors.initials: CA
authors.lastname: Bona
authors.forename: J
authors.initials: J
authors.lastname: Schulman
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis*; D017353:Gene Deletion; D005803:Genes, Immunoglobulin; D006386:Hemagglutination Tests; D007147:Immunoglobulin Light Chains / Q000235:genetics / Q000276:immunology*; D007145:Immunoglobulin kappa-Chains / Q000235:genetics / Q000276:immunology; D007146:Immunoglobulin lambda-Chains / Q000276:immunology; D008168:Lung / Q000821:virology; D051379:Mice; D008969:Molecular Sequence Data; D009975:Orthomyxoviridae / Q000276:immunology*; D009976:Orthomyxoviridae Infections / Q000517:prevention & control*; D016019:Survival Analysis; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014611:Vaccination; D014771:Virion / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D007147:Immunoglobulin Light Chains; D007145:Immunoglobulin kappa-Chains; D007146:Immunoglobulin lambda-Chains