Variable region gene selection of immunoglobulin G-expressing B cells with specificity for a defined epitope on type II collagen.
Immunization with type II collagen (CII) induces collagen-induced arthritis (CIA) in animals, and B cells reactive with CII are involved in the induction and manifestation of the disease. In this study, B cell hybridomas producing IgG antibodies specific for a major epitope on mouse CII (the "C1" epitope, amino acid 316-333), were isolated 11 days after immunization from draining lymph nodes in DBA/1 mice. Injection into neonatal mice of purified and biotinylated monoclonal antibodies binding the C1 epitope led to a specific binding to joint cartilage, demonstrating that the antibodies interact with native antigen in vivo. cDNA sequencing of the B cell clones revealed that they all expressed the same combination of a variable heavy chain (VH J558 family) and light chain (V kappa 21 family) germ-line gene, apparently lacking somatic mutations. The presence of isotype-switched B cells expressing a certain combination of V genes encoding antibodies that bind epitopes in vivo, indicates that this B cell population has been peripherally selected.
Mo
J A
JA
Department of Medical and Physiological Chemistry, Uppsala University, Sweden.
Bona
C A
CA
Holmdahl
R
R
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000235:genetics; D000918:Antibody Specificity; D001168:Arthritis / Q000209:etiology / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D001483:Base Sequence; D003094:Collagen / Q000276:immunology*; D004247:DNA / Q000235:genetics; D000939:Epitopes; D005803:Genes, Immunoglobulin; D006825:Hybridomas / Q000276:immunology; D007074:Immunoglobulin G / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D051379:Mice; D008811:Mice, Inbred DBA; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid
D000911:Antibodies, Monoclonal; D000939:Epitopes; D007074:Immunoglobulin G; D007135:Immunoglobulin Variable Region; D003094:Collagen; D004247:DNA