title: Rearrangement of mouse immunoglobulin kappa deleting element recombining sequence promotes immune tolerance and lambda B cell production.
abstract: The recombining sequence (RS) of mouse and its human equivalent, the immunoglobulin (Ig) kappa deleting element (IGKDE), are sequences found at the 3' end of the Ig kappa locus (Igk) that rearrange to inactivate Igk in developing B cells. RS recombination correlates with Ig lambda (Iglambda) light (L) chain expression and likely plays a role in receptor editing by eliminating Igk genes encoding autoantibodies. A mouse strain was generated in which the recombination signal of RS was removed, blocking RS-mediated Igk inactivation. In RS mutant mice, receptor editing and self-tolerance were impaired, in some cases leading to autoantibody formation. Surprisingly, mutant mice also made fewer B cells expressing lambda chain, whereas lambda versus kappa isotype exclusion was only modestly affected. These results provide insight into the mechanism of L chain isotype exclusion and indicate that RS has a physiological role in promoting the formation of lambda L chain-expressing B cells.
authors.affiliation: Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: José Luis
authors.initials: JL
authors.lastname: Vela
authors.forename: Djemel
authors.initials: D
authors.lastname: Aït-Azzouzene
authors.forename: Bao Hoa
authors.initials: BH
authors.lastname: Duong
authors.forename: Takayuki
authors.initials: T
authors.lastname: Ota
authors.forename: David
authors.initials: D
authors.lastname: Nemazee
mesh_terms: D000818:Animals; D000974:Antibodies, Antinuclear / Q000097:blood; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D015328:Gene Rearrangement, B-Lymphocyte, Light Chain / Q000235:genetics* / Q000276:immunology; D005803:Genes, Immunoglobulin; D006825:Hybridomas; D007108:Immune Tolerance; D007145:Immunoglobulin kappa-Chains / Q000235:genetics* / Q000276:immunology*; D007146:Immunoglobulin lambda-Chains / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2; D011995:Recombination, Genetic
chemical_list: D000974:Antibodies, Antinuclear; D007145:Immunoglobulin kappa-Chains; D007146:Immunoglobulin lambda-Chains; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; C052617:Bcl2 protein, mouse