Combinational diversity within variable regions bearing the predominant anti-ρ-azophenylarsonate idiotype of strain a mice

Academic Article

Abstract

  • The humoral immune response in strain A mice to protein conjugates of ρ-azophenylarsonate (Ars) is characterized by the presence of a major cross-reactive idiotype denoted as Id(CR). Previous molecular analyses of monoclonal Id(CR+) Ars-binding antibodies isolated from multiply immunized animals have indicated that these antibody variable (V) regions may be the expressed product of a single combination of V(H), D, J(H), V(K), and J(K) gene segments. The basis of this apparent domination of the Ars response by V regions encoded by this single combination of gene segments is unclear, but is discussed in this report. Our structural analyses on five monoclonal Id(CR+) antibodies that are unable to bind Ars show that in contrast to those of Ars-binding ID(CR+) antibodies that are unable to bind Ars show that in contrast to those of Ars-binding Id(CR+) antibodies, these (Ars-nonbinding) Id(CR+) V regions are encoded by multiple combinations of V(H), D, J(H), V(K), and J(K) gene segments, but with the commonality that they all utilize a single V(H) gene segment (V(H)Id(CR)). We provide examples in which the V(H)Id(CR) gene segment is expressed with three different V(K) gene segments and with each of the four J(H) gene segments to produce serologically detectable Id(CR+) Ars-nonbinding antibodies. It would thus appear that the previous failure to detect alternative Id(CR+) Ars-nonbinding antibodies. It would thus appear that the previous failure to detect alternative Id(CR+) V segment combinations was due to a sampling procedure requiring that the Id(CR+) antibody bind Ars, and not the results of restricted assembly or expression of the V(H)Id(CR) gene segment with a particular combination of D, J(H), V(K), and J(K) gene segments. This bias in protocol, however, cannot completely account for the homogeneity in previously studied Id(CR+) Ars-binding antibodies, because we were able to isolate, from primary immune responses, Id(CR+) Ars-binding antibodies, that do bind Ars but that utilize alternative V segment combinations. This finding suggests that combinations of V gene segments encoding Id(CR+) antibodies are more numerous in primary as opposed to secondary immune responses, and raises the question of why a single combination of V(H), D, J(H), V(K) gene segments dominates the secondary strain A immune response to Ars.
  • Authors

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    Author List

  • Wysocki LJ; Margolies MN; Huang B; Nemazee DA; Wechsler DS; Sato VL; Smith JA; Gefter ML
  • Start Page

  • 2740
  • End Page

  • 2747
  • Volume

  • 134
  • Issue

  • 4