The Genetic Control of Response to Antigenic Stimuli

Abstract

The level of secondary antibody response to Tobacco Mosaic Virus (T.M.V.) is shown to be a highly heritable characteristic (h² = 0.876, σ = 0.09) in a cross-bred population of rabbits. The secondary response to Bovine Plasma Albumin (B.P.A.) does not show any such heritability; variation as measured under our experimental conditions could all be assigned to environmental differences. However, diffusion tests demonstrate that this antigen has at least 7 reactive components, 2 of which are due to a globulin contaminant. In these circumstances, it is suggested that the “experimental error” deriving from the complexity of the antigen make any estimation of heritability impossible. A proportion of the rabbit population showed no response to B.P.A., even when given in massive doses. This failure to produce antibodies is probably due to a recessive gene (or genes) segregating in the population. Animals of this genotype retain the antigen in their circulation for an abnormally long time. Response in normal animals follows immediately on the disappearance of circulating antigen, but this reaction apparently does not occur in the abnormal group. Response to the other antigens tested, except possibly to globulins, was not affected by this “genetic block”. Correlations were found between response to T.M.V. and Diphtheria toxoid (D.t.) (r = 0.5, σ = 0.15) and to T.M.V. and Bovine Red Cells (r = 0.54, σ = 0.24). No correlations could be demonstrated for responses to Shigella Shiga, Bushy Stunt Virus, Human Red Cells, or Tetanus toxoid (T.t.) But the complex nature of these antigens makes this negative evidence inconclusive. Rabbits tested with all these antigens showed a significant tendency to produce related responses to different antigens, suggesting that they have a general predisposition to respond at some inherent level to all antigenic stimuli. Primary and secondary responses to D.t. are shown to be correlated, as are primary responses to D.t. and to T.t. Pregnant or lactating rabbits show a significantly lowered response to D.t. and to T.t. The importance of genetic constitution in determining ability to produce antibodies is discussed, and some of the necessary conditions for further work on this subject are defined.