Antigen binding and idiotype analysis of antibodies obtained after electroporation of heavy and light chain genes encoding phosphocholine-specific antibodies : a model for T15-idiotype dominance

• Published in: The Journal of experimental medicine Vol. 176; no. 6; pp. 1637 - 1643
• Main Authors: KENNY, J. J, MORATZ, C. M, LONGO, D. L, GUELDE, G, O'CONNELL, C. D, GEORGE, J, DELL, C, PENNER, S. J, WEBER, J. S, BERRY, J, LATHAM CLAFLIN, J
• Format: Journal Article
• Language: English
• Published: New York, NY Rockefeller University Press 01.12.1992; The Rockefeller University Press
• Subjects: Amino Acid Sequence; Animals; Antibodies, immunoglobulins; Antibody Formation; Antibody Specificity; Antigen-Antibody Complex; Base Sequence; Biological and medical sciences; Cell Line; Electric Stimulation; Enzyme-Linked Immunosorbent Assay; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Genes, Dominant; Genes, Immunoglobulin; Genetic markers (allotypes, idiotypes); Immunoglobulin Heavy Chains - biosynthesis; Immunoglobulin Heavy Chains - genetics; Immunoglobulin Heavy Chains - metabolism; Immunoglobulin Idiotypes - biosynthesis; Immunoglobulin Idiotypes - genetics; Immunoglobulin Idiotypes - metabolism; Immunoglobulin Light Chains - biosynthesis; Immunoglobulin Light Chains - genetics; Immunoglobulin Light Chains - metabolism; Immunoglobulin Variable Region - genetics; Mice; Mice, Inbred Strains; Molecular immunology; Molecular Sequence Data; Phosphorylcholine - immunology; Rats; Nucleotide sequence; Antibody; heavy-Peptide chain; Rodentia; light-Peptide chain; Electroporation; Antigen; Immunogenetics; Vertebrata; Specificity; Mammalia; Binding capacity; Gene; Mouse; Germ line; Gene rearrangement; Idiotype
• ISSN: 0022-1007; 1540-9538
• DOI: 10.1084/jem.176.6.1637

Antibodies bearing the T15 idiotype dominate the murine primary immune response to phosphocholine (PC). Analysis of antigen binding of antibodies derived from V1:DFL16.1:JH1 (VH1) germline and N region-derived variant heavy (H) chains and kappa 22, kappa 24, and kappa 8 light (L) chains demonstrates that the T15H:kappa 22L (T15) antibody binds PC at least 20-40 times better than other antibodies derived from alternate germline forms of the VH1 H chain and kappa 22, kappa 24, or kappa 8 L chains. To achieve affinities in the same range as the T15 antibody, kappa 24 and kappa 8 L chain-containing antibodies must have H chains derived from variant N region or somatically mutated VH1 genes. Single amino acid differences at the VD junction of the various germline and N region variant VH1 H chains dictate the L chain that can associate with the H chain to produce a PC-specific antibody. Several H:L combinations give rise to T15 or M167 idiotype-positive antibodies that lack specificity for PC, and single amino acid substitutions or insertions at the VH1:D junction result in the loss of T15 or M167 idiotopes. Based on these observations, our data support a molecular model involving both preferential gene rearrangement and antigen-driven B cell selection to explain T15 idiotype dominance in the immune response to PC. In the absence of N region diversification, large numbers of neonatal B cells bearing the T15H:kappa 22L surface immunoglobulin M (sIgM) receptors would be selected and expanded by autologous or environmental PC antigen into the long-lived peripheral B cell pool.