title: A point mutation in the constant region of Ig lambda1 prevents normal B cell development due to defective BCR signaling.
abstract: Surface expression of B cell antigen receptors (BCRs) containing Ig and Igalpha/Igbeta generates signals required to transit discrete developmental checkpoints. The mechanism by which BCR components collaborate to initiate signals is still unclear. The expression of Iglambda1 in SJL mice is 50-fold lower than in other strains. Here, we demonstrate by gene targeting that a point mutation, which changes a glycine to a valine in the lambda1 constant region, is responsible for this defect. In vitro experiments show that Ig receptors bearing this mutation, while expressed normally, are deficient in signaling. These findings reveal a direct involvement of the Ig light chain (IgL) in B cell signaling and development beyond the requirement of light chains for BCR assembly.
authors.affiliation: Department of Molecular Genetics and Cell Biology, University of Chicago, IL 60637, USA.
authors.forename: Tianhe
authors.initials: T
authors.lastname: Sun
authors.forename: Marcus R
authors.initials: MR
authors.lastname: Clark
authors.forename: Ursula
authors.initials: U
authors.lastname: Storb
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology*; D001854:Bone Marrow Cells / Q000166:cytology; D002454:Cell Differentiation; D003432:Cross-Linking Reagents; D015328:Gene Rearrangement, B-Lymphocyte, Light Chain; D018390:Gene Targeting; D005803:Genes, Immunoglobulin / Q000502:physiology*; D005998:Glycine / Q000235:genetics / Q000502:physiology; D007127:Immunoglobulin Constant Regions / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D007133:Immunoglobulin Joining Region / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D007146:Immunoglobulin lambda-Chains / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D018655:Lymphocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D017853:Phosphotransferases (Alcohol Group Acceptor); D017354:Point Mutation; D017434:Protein Structure, Tertiary; D011947:Receptors, Antigen, B-Cell / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D011995:Recombination, Genetic; D015398:Signal Transduction; D013154:Spleen / Q000166:cytology; D014633:Valine / Q000235:genetics / Q000502:physiology
chemical_list: D003432:Cross-Linking Reagents; D007127:Immunoglobulin Constant Regions; D007133:Immunoglobulin Joining Region; D007135:Immunoglobulin Variable Region; D007146:Immunoglobulin lambda-Chains; D011947:Receptors, Antigen, B-Cell; D017853:Phosphotransferases (Alcohol Group Acceptor); C023916:phosphoglycerol kinase; D014633:Valine; D005998:Glycine