Antibodies and Myeloma Proteins Used in These Studies Use Antibody

Studies of the various kinds of immunoglobulin (Ig) allotype and isotype suppressions induced by perinatal exposure to anti-Ig antibodies have yielded many valuable insights into the normal processes that control B cell differentiation and expression. For example, the demonstration that exposure to antibodies to an IgG isotype specifically suppresses production of that isotype, whereas the exposure to antibodies to IgM suppresses production of IgM and all IgG isotypes provided the first outlines of the precursor-progeny relationships in the B cell development pathway (1, 2). Similarly, the proof that suppressor T cells regulate antibody production rests in part on the highly specific suppression of allotype-marked adoptive secondary antibody responses demonstrable with suppressor T cells induced by perinatal exposure to antiallotype antibodies (3, 4). Thus, although the mechanisms responsible for suppression induction during the neonatal period are of interest per se, the properties of the suppressions induced by different kinds of antibody exposures frequently offer more broadly applicable information. At least three characteristic patterns of allotype suppression have been described in allotype heterozygotes exposed to antibodies reactive with paternal Ig allotypes. In rabbits, the antibodies commonly used for suppression induction react with Ig light chain or Ig heavy chain variable-region determinants present on most of the Ig in serum in homozygotes and a little less than one-half the serum Ig in heterozygotes. After perinatal antiallotype exposure, B cells bearing the target allotype are depleted and gradually recover. Paternal allotype levels in serum remain low well after the allotype-bearing B cells return; however, older suppressed animals (>6-mo-old) usually initiate and maintain substantial serum allotype production. In general, the suppression of paternal allotype production is accompanied by a compensatory increase in maternal serum-allotype levels that return to normal when suppression is relieved (5-8). In the mouse, antiallotype antibodies almost exclusively detect Ig heavy chain constant-region determinants and thus are restricted to reaction with allotypes represented on one or occasionally two Ig isotypes (9). The suppression induced by these antiallotype antibodies appears similar to the suppression induced by heterologous anti-isotype antibodies except that production of only one of the two allotypes in the heterozygote is affected (1, 2, 10-12).