Studies of the Development of a Normal Antibody and of Cellular Antigens in the Blood of Sheep
Authors: Ycas Mary K. Warren 
Published: January 2023

Summary
Nine reagents detecting in sheep cells the apparently independent cellular antigens, called A, B, C, D, E, F, G, H and K, have been prepared from antiserum obtained by immunizations of sheep and rabbits. These nine cellular characters are presumed to be gene determined and dominant, although critical genetic data to establish this point are not yet available.
Two normally occurring antibodies in the serum of certain sheep, and their corresponding antigens in the blood cells of other individuals, have been noted. Based upon the reactions of the serum and cells of 133 adults, sheep may be classified into (a) those which possess the antigen called R, and (b) those which do not possess R but whose sera contain anti-R. The gene (R) for the R antigen is dominant to the (rr) for its absence on the cells and the presence of the anti-R hemolysin. The existence of a gene (r) for a third class which possesses neither antigen nor antibody is highly improbable.
The R antigen was not detectable on the cells of newborn lambs, but usually appeared between the second and third week after birth. Following its first appearance, it was remarkably constant. On the other hand, the cellular characters reacting with the immune reagents were established on the cells at birth. The serum from R sheep—but not those with anti-R—specifically inhibited the reaction between R cells and the anti-R hemolysin. In contrast to this, there was no inhibition of the immune reagents with serum from sheep whose cells bore the corresponding specific antigen. At birth the serum from a lamb belonging to the R group would inhibit the R-anti-R reaction, even though the R antigen could not be detected on the cells.
The anti-R hemolysin was not present in the serum of a lamb at birth, but appeared soon after the ingestion of colostrum. This passively transferred antibody persisted in the serum of a young lamb for a variable length of time. The age at which the antibody appeared which was formed by the lamb itself was also variable. The titer of this hemolysin varied considerably among individual sheep as well as for the same individual at different times.
The level of total protein in the blood serum of many lambs was determined, and it was observed that the appearance of anti-R in the very young lamb corresponded with the rise in the level of serum protein after birth; its disappearance paralleled the drop caused by the decrease in globulin concentration. In the study of lambs belonging to the R group, it was more difficult to assess the possible significance of a correlation between the development of the R antigen on the cells and the changes in the serum protein. However, the suggestion is made that there may be a relation between the titer of anti-R inhibiting substance in the serum and the serum protein concentration, and that there may be an association between the time of establishment of the relative concentration of all the protein components as observed in the serum of young adults and the first appearance of demonstrable R antigen on the erythrocytes.