IN VITRO STUDIES ON ALLOTYPE SUPPRESSION III. Components of Antiallotype Serum Active in Release from Allotype

In rabbits which are heterogeneous with respect to antigenic determinants on serum immunoglobulins (Ig), prenatal or neonatal exposure to antibodies specific for one allelic allotype leads to a long-lasting suppression of that type with compensatory production of the alternate allelic product. This phenomenon, called allotype suppression, was first described by Dray in 1962 (1) . Although many studies since then have amply verified and further characterized Dray's original observations (reviewed by Mage in reference 2), the mechanism of suppression remains obscure . By using specific antiallotype sera it has been possible to identify b locus determinants on T2-neutralizing antibodies formed by spleen cells of heterozygous rabbits in vitro and to demonstrate that cells from b4b5 rabbits which were deficient in their ability to produce b4 Ig because of exposure to anti-b4 in utero formed anti-T2 antibodies which appeared to be entirely of the nonsuppressed type, namely, b5 (3) . However, when such cells were cultured in the presence of anti-b5 serum made in b4 rabbits, b5 anti-T2 production was suppressed, while highly significant amounts of b4 anti-T2 were formed, indicating that the anti-b5 serum had caused release of the mechanism responsible for allotype suppression . In the present study, the more general applicability of this phenomenon has been verified by culturing the spleen cells of b4-suppressed b4b6 rabbits with b4 anti-b6 serum . Results entirely analogous to those previously observed with the b4b5 system are reported . A further extension of the experimental conditions for bringing about the reversal of b4 suppression by using other rabbit antisera specific for the nonsuppressed type has revealed the participation of two factors in this process : antibody activity against the nonsuppressed allotype and normal b4 Ig .