Polymorphism in anti-phosphocholine antibodies reflecting evolution of immunoglobulin families.
Complete variable (V) region amino acid sequences were determined for four heavy (H) and one light (L) chain from C57BL phosphocholine (PC)-binding monoclonal antibodies. Additional NH2-terminal sequences were obtained from H and L chains of C57BL and CBA/J origin. When these V regions were compared with previously reported anti-PC sequences, a number of observations could be made regarding the function and evolution of L and H chain segments used in these antibodies. (a) L and H chain V segments are remarkably conserved in these inbred strains, although there has been an accumulation of point mutations identifying apparently allelic forms of VK and VH. (b) Mice of each genotype use the same three VK segments in combination with a single VH segment to produce most anti-PC antibodies. An exception has been noted that indicates the occasional use of a second VH gene segment. (c) Multiple, different DH regions are used by mice of each strain, which suggests that the DH segment sequence plays no critical role in either antigen binding or VH-VL pairing. Furthermore, the DH segments and their corresponding gene families appear to be highly conserved in the inbred strains studied. (d) Most PC-binding antibodies use the JH1 joining segment. All JH1 sequences from C57BL mice differ from the BALB/c JH1 at position 105, which identifies allelic forms of the JH1 region. These studies are a first assessment of the nature of mutational events associated with the evolution of specific multigene immunoglobulin families and indicate that homologous VH, DH, JH, VK, and JK genes are similarly assembled and expressed in PC antibodies from three diverse genotypes.
D000595:Amino Acid Sequence; D000818:Animals; D000916:Antibody Diversity; D001666:Binding Sites, Antibody / Q000235:genetics*; D005075:Biological Evolution; D002794:Choline / Q000031:analogs & derivatives*; D006825:Hybridomas / Q000276:immunology; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007147:Immunoglobulin Light Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D051379:Mice; D008815:Mice, Inbred Strains / Q000235:genetics* / Q000276:immunology; D010767:Phosphorylcholine / Q000276:immunology*; D011110:Polymorphism, Genetic
D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D007135:Immunoglobulin Variable Region; D010767:Phosphorylcholine; D002794:Choline