Allotype Synthesis I. Chronic Suppression after Perinatal Exposure to Maternal Antibody to Paternal Allotype in (sjl

Allotype suppression is a unique example in higher organisms of the regulation of gene expression by antibodies directed against the product of those genes. Both in rabbits and mice, prenatal and/or early postnatal exposure to anti-immunoglobulin allotype antibody suppresses production of the allotype in animals genetically capable of producing it. However, the long-lived or "chronic" suppression often observed in rabbits (1-4) contrasted sharply with the short-lived allotype suppression reported in mice (5). In the mouse intercross previously studied (BALB/c X C57BL/10), allotype heterozygotes, sired by normal (Igb) 1 males mated with (Ig a) females immune to the paternal (Ig-lb) allotype, exhibited an initial delay in the appearance of the Ig-lb immunoglobulins and continued to have less than normal levels of these immunoglobulins for some time. However, the delay was in the order of only a few weeks and the suppressed allotype reached near-normal levels by 12-14 wk after birth. The reasons for this major difference between mouse and rabbit have been difficult to understand. We have now observed, using a different paternal strain (also Igb), that chronic suppression can be obtained in mice as well. The studies presented in this publication show that the suppression of Ig-lb production in Ig~/Ig b hybrids derived from the mating of SJL (Ig b) males with BALB/c (Ig ") females immunized to Ig-lb is much more long lasting. In about half the mice there is no paternal Ig-lb immunoglobulin detectable as late as 6-9 months of age, although transient production of Ig-lb occurs in a majority of these mice before this time. The mechanism of allotype suppression is not known, but a commonly held view is that it is analogous to specific immunological tolerance, i. e., that cells committed to production of the suppressed allotype are eliminated or diverted from production of