Regulation of allotype expression in heterozygous rabbits. III. Concomitant modulation and concomitant suppression oa...

Sensitization of peripheral blood lymphocytes from heterozygous a2/a3 rabbits with purified, monospecific anti-a3 antibodies, raised in a1/a1 rabbits, resulted in the disappearance of surface a2 and a3 allotypes (concomitant modulation) after subsequent incubation at 37 degrees C, as determined by the mixed antiglobulin (rosette) test. Similar results were obtained when anti-a2 antibodies were used. The dose dependence of modulation and comodulation were also studied. Testing of mixtures of homozygous a2/a2 plus a3/a3 cells never led to comodulation. Blocking studies, performed to determine the surface contiguity of a2 and a3 determinants, indicated that both allotypes are situated close together in the membrane on cells exhibiting allotype inclusion. Overnight culture in serum-free medium revealed that cells which underwent extensive modulation and comodulation were often suppressed for both homologous and alternate allotypes (concomitant suppression). These and other data suggest that a single modulation event, in which extensive removal of cell membrane Ig occurred, could serve to inhibit the re-expression of Ig. This may, in part, reflect interactions with membrane receptors involved in the regulation of expression of VH gene products. Implications of VH allotype inclusion are discussed.