I M M U N O G L O B U L I N S Y N T H E S I S I N M I C E Suppression by Anti-allotype Antibody*

Differentiation of the immune system poses the following novel problems in control of expression of genetic material. For all autosomal loci, expression of a locus in a given cell always means expression of both alleles at the locus; however, immunoglobulin loci although autosomal, do not conform to this rule (1). Mature plasma (antibodyproducing) cells produce immunoglobulins specified by only one or the other of the two alleles at the immunoglobulin locus being expressed by the ceils; e.g. in mice, for a cell making 7G~a, the cell produces either Ig-la or Ig-lb (2). Although much is known about X-chromosome inactivation (the "Lyon effect") (3), there is little to suggest how and when a single autosome, or part of an autosome, may be selectively inactivated in a cell. Studies presented in this paper on the suppression of production of allotype in young animals exposed to antibody reacting with the allotype have yielded results bearing on this question of the committment of a cell to production of a single allotype. Following the demonstration by Dray (4) that severe prolonged suppression of the synthesis of paternal gamma globulin isoantigen (aUotype) resulted from the gestation of a heterozygous rabbit in a mother immune to the paternal allotype, the attention of several laboratories focused on the effects on mother and/or fetus of immunoglobulin incompatibilities. Mage and Dray (5) have shown that the depression of synthesis after exposure to anti-paternal allotype antibody is evident for up to 3 yr. In the same publication they showed that similar depression could be obtained by injection of anti-paternal allotype at birth. Dubiski and Fradette (6) confirm this latter result in a more recent publication. Attempting to extend this work to the mouse, Lieberman and Dray (7) were unable to demonstrate a similar suppression of paternal allotype in response to maternal anti-paternal antibody. The majority of their offspring from immune mothers died either at birth or just prior to birth under conditions where the mother appeared unable to deliver the litter normally. Of the survivors, all appeared to have normal levels of paternal allotype. In contrast with Lieberman and Dray, we have been able to demonstrate, in the hybrid mouse, suppression of paternal allotype production in response to maternal