Molecular characterization of antibodies bearing Id-460. I. The structure of two highly homologous V(H) genes used to produce idiotype positive immunoglobulins

The heavy chain immunoglobulin genes encoding a variety of antibodies specific for DNP or Pasteurella pneumotropica and bearing the dominant idiotype of MOPC 460, Id-460, were cloned and sequenced. The V(H) genes encoding the M460 and D35 (DNP binding) antibodies were found to be homologous but not identical to the V(H) gene encoding the LB8 (P. pneumotropica binding) monoclonal antibody. Two of at least eight genes in the V(H460) cross-hybridizing gene family can encode Id-460 positive antibodies. The V(H460) gene family overlaps with the gene family described by V(H36-60) and more completely describes this germ-line V(H) gene family. We have previously demonstrated a genetic requirement for V(K1) expression in order to observe the expression of Id-460 in anti-DNP antibody responses. Southern blot analysis of these monoclonal antibody-producing cells demonstrates, as with the cross-hybridizing V(H), that two cross-hybridizing V(K1) genes (V(K1A) and V(K1C)) can be used to encode Id-460-positive immunoglobulins. We demonstrate that immunoglobulin idiotype determinant expression can be the result of the expression of nonidentical but highly homologous genes in the V(H460) cross-hybridizing V(H) gene family and also in the V(K1) cross-hybridizing V(L) family.