title: Antibody response elicited by T-dependent and T-independent antigens in gene targeted kappa-deficient mice.
abstract: Animal models substantially contribute to the understanding of the pathogenesis of various human diseases, including those associated with genetic defects. Our study investigated the characteristics of antibody responses elicited by T-dependent and T-independent antigens in mice rendered kappa-deficient by targeted deletion of the J kappa C kappa gene segments. It is known that in normal murine species the kappa repertoire dominates the antibody repertoire (kappa/lambda ratio = 95:5). Our results indicate that the kappa gene deletion causes the alternative usage of lambda 1 (93%) and lambda 2 (7%) light chains, confirming previous studies demonstrating that in kappa-deficient mice all B cells express Ig lambda receptors. The anti-trinitrophenylbenzene (TNP) response in K-/- mice was compensated for by lambda 1 and lambda 2 bearing Igs. However, isoelectric focusing analysis of anti-TNP antibodies showed a considerably more restricted pattern of lambda anti-TNP antibodies in K-/- as compared with kappa antibodies in normal mice. No major differences were observed in the affinity for the hapten of kappa or lambda 1 or lambda 2 mAbs obtained from 129/Sv and K-/- mice. Furthermore, lambda 1 and lambda 2 chains can reconstitute the expression of an idiotype (460Id) borne on kappa anti-TNP antibodies. The 460Id was detected both in polyclonal and monoclonal anti-TNP antibodies obtained from K-/- mice. Our results clearly showed that the kappa anti-TNP repertoire is compensated by the lambda repertoire even though the latter is clonally restricted in K-/- mice.
authors.affiliation: Mount Sinai School of Medicine, New York, NY 10029.
authors.forename: L
authors.initials: L
authors.lastname: Pricop
authors.forename: T
authors.initials: T
authors.lastname: Brumeanu
authors.forename: E
authors.initials: E
authors.lastname: Elahi
authors.forename: T
authors.initials: T
authors.lastname: Moran
authors.forename: B S
authors.initials: BS
authors.lastname: Wang
authors.forename: M
authors.initials: M
authors.lastname: Troustine
authors.forename: D
authors.initials: D
authors.lastname: Huszar
authors.forename: F
authors.initials: F
authors.lastname: Alt
authors.forename: C
authors.initials: C
authors.lastname: Bona
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000917:Antibody Formation / Q000276:immunology*; D000955:Antigens, T-Independent / Q000276:immunology*; D004406:Dysgammaglobulinemia / Q000276:immunology*; D000939:Epitopes / Q000276:immunology*; D006241:Haptens; D006433:Hemocyanins / Q000276:immunology; D007145:Immunoglobulin kappa-Chains / Q000276:immunology*; D007146:Immunoglobulin lambda-Chains / Q000276:immunology; D007525:Isoelectric Focusing; D051379:Mice; D008817:Mice, Mutant Strains; D013601:T-Lymphocytes / Q000276:immunology*; D014301:Trinitrobenzenes / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D000955:Antigens, T-Independent; D000939:Epitopes; D006241:Haptens; D007145:Immunoglobulin kappa-Chains; D007146:Immunoglobulin lambda-Chains; D014301:Trinitrobenzenes; C054401:trinitrophenyl keyhole limpet hemocyanin; D006433:Hemocyanins