Induction of "latent a2" allotype in a1a1 homozygous rabbits as the major part of a bidirectional immune response to immunization with anti-a2 antibody.

Abstract

Previously, we induced Ab to a common idiotypic specificity (IdC) of rabbit anti-a2 VH Ab. We observed then that some of the putative anti-IdC Ab molecules induced by immunizing a1a1 rabbits with anti-a2 Ab did not have the expected nominal allotypic markers (a1, x32, or y33) characteristic of the genotype of the immunized rabbits. Thus, immunization of a1 a1 rabbits with a1 anti-a2 Ab induced population of molecules that reacted with anti-a2 Ab but bore an unidentified (unknown) VH region marker. The following observations indicate that these molecules bear a "latent a2" allotypic marker: (a) when the unknown VH molecules were used to immunize a1 a1 and a3 a3 rabbits, anti-a2 Ab was produced; (b) when an a2 a2 rabbit was immunized with the same preparation of unknown VH molecules, an anti-idiotypic Ab was produced; and (c) when the unknown VH molecules were used to inhibit the binding of labeled a2 IgG to anti-a2 Ab, the inhibition curve obtained was essentially the same as that obtained by using normal a2 IgG. Thus, immunization of a1 a1 rabbits with a1 anti-a2 Ab provided a bidirectional stimulus to produce both nominal "a1" anti-IdC Ab and a "latent a2" allotype. The distribution of nominal to latent allotypes induced ranged from 3% nominal/92% latent to 57% nominal/23% latent. In absolute terms, the maximum amount of "latent a2" molecules was 1.18 mg/ml of serum, which far exceeds the amount of latent allotype described by others (0.3 mg/ml of serum). The effective induction of large amounts of "latent a2" allotype may have resulted from a simultaneous stimulation of an idiotope and a paratope on the surface of the "latent a2"-producing cells.