title: Combinatorial immunoglobulin light chain variability creates sufficient B cell diversity to mount protective antibody responses against pathogen infections.
abstract: To analyze how combinatorial light (L) chain diversity influences the B cell repertoire, we studied mice with a homozygous immunoglobulin-heavy-chain null mutation (mu MT), in which the B cell developmental block was overridden by the expression of a transgenic immunoglobulin mu heavy (H) chain derived from a vesicular stomatitis virus Indiana serotype (VSV-IND)-neutralizing Ab (T11 mu MT mice). The randomly integrated transgene could not undergo secondary rearrangements and was expressed in combination with endogenous kappa or lambda chains. T11 mu MT mice had a skewed B cell repertoire as evidenced by 30-60% VSV-IND-specific peripheral B cells and spontaneous VSV-IND-neutralizing serum titers. Upon immunization, T11 mu MT mice mounted specific IgM antibody responses against VSV-IND but, interestingly, they also responded against VSV New Jersey serotype (VSV-NJ), lymphocytic choriomeningitis virus, poliovirus and Salmonella typhi porins. Variable-region sequence analysis revealed that VSV-NJ-specific antibodies expressed numerous L chains in combination with the transgenic H chain, which was devoid of hypermutations. Thus, in T11 mu MT mice combinatorial L chain variability alone is able to build up a sufficiently complex B cell repertoire to mount protective immunoglobulin responses against a variety of pathogens.
authors.affiliation: Institute of Experimental Immunology, Department of Pathology, University Hospital Zürich, Switzerland.
authors.forename: Beatrice M
authors.initials: BM
authors.lastname: Senn
authors.forename: Constantino
authors.initials: C
authors.lastname: López-Macías
authors.forename: Ulrich
authors.initials: U
authors.lastname: Kalinke
authors.forename: Alain
authors.initials: A
authors.lastname: Lamarre
authors.forename: Armando
authors.initials: A
authors.lastname: Isibasi
authors.forename: Rolf M
authors.initials: RM
authors.lastname: Zinkernagel
authors.forename: Hans
authors.initials: H
authors.lastname: Hengartner
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood / Q000235:genetics*; D000916:Antibody Diversity; D000956:Antigens, Viral / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D015328:Gene Rearrangement, B-Lymphocyte, Light Chain; D007147:Immunoglobulin Light Chains / Q000235:genetics*; D007148:Immunoglobulin mu-Chains / Q000235:genetics; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009500:Neutralization Tests; D010641:Phenotype; D017955:Poliovirus / Q000276:immunology; D018272:Porins / Q000276:immunology; D018353:Rhabdoviridae Infections / Q000276:immunology; D012485:Salmonella typhi / Q000276:immunology; D014721:Vesicular stomatitis Indiana virus / Q000145:classification / Q000276:immunology; D018116:Vesiculovirus; D014777:Virus Diseases / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral; D007147:Immunoglobulin Light Chains; D007148:Immunoglobulin mu-Chains; D018272:Porins