Ontogeny of Immunological Properties 



563 



eggs to the 48-hour pluteus. From the results 

 of absorption experiments they conclude 

 that there are, in addition, antigens present 

 in the 48-hour embryos that are not detect- 

 able in the earlier stages tested (unfertilized 

 eggs, 4-hour and 12-hour embryos). On the 

 other hand, none of the antigens detectable 

 in eggs and early embryos appears to be 

 lost in the later embryo. These workers also 

 examined vegetalized 48-hour embryos, pro- 

 duced as a result of lithium treatment, and 

 found no antigenic difference from the nor- 

 mal plutei. By means of the Ouchterlony ('49, 

 see also Jennings and Malone, '54) technique, 

 of diffusion in agar plates, Perlmann ('53) 

 finds that extracts of the different develop- 

 mental stages of the sea urchin possess mostly 

 common antigens that are also of similar con- 

 centration. Harding et al. ('54), using this 

 method with hybrid embryos, report the ap- 

 pearance of "paternal" antigens at a stage be- 

 fore the morphological traits can be easily 

 detected. 



In the Cecropia silkworm Telfer and Wil- 

 liams ('53) describe, in addition to five per- 

 sistent antigens, one that appears in the blood 

 of fifth instar larvae and disappears during 

 adult development. Telfer ('54) finds an anti- 

 gen in advilt female blood that is undetectable 

 in larvae and almost so in adult males but 

 present in the yolk of unfertilized eggs. 



The variovis investigations described above 

 are more in accord in regard to antigenic 

 resemblances than in regard to differences 

 at various stages in development. They do 

 not rule out the possibility that all antigenic 

 structures are represented in the uncleaved 

 egg and only changes in quantity and loca- 

 tion (i.e., distribution to different chemical 

 substances and to different tissues) occur 

 during development. This question will be 

 considered further after presentation of ex- 

 periments on blood cell antigens. 



ANTIGENS OF VERTEBRATE BLOOD 

 CELLS 



In humans the A and B isoagglutinogens 

 have been detected in the erythrocytes of 

 the month-old fetus and the M and N ag- 

 glutinogens at the second month (see 

 Wiener, '43, for references). Presumably 

 these may be present in earlier stages that 

 have not been tested. In rabbits the agglutin- 

 ogens Hj and Ho have been found as early 

 as the 4 mm. stage (Keeler and Castle, '34), 

 at which time the erythrocytes are still 

 nucleated. According to the early work it 

 would seem that all the blood cell antigens 



appeared on the cells as soon as they were 

 formed. However, there are recent experi- 

 ments in which some cellular antigens have 

 been found to appear rather late. Briles, 

 McGibbon and Irwin ('48) studied chicken 

 red cell antigens the inheritance of which 

 is determined by two series of multiple al- 

 lelic genes. The antigens determined by one 

 series were all found in embryos of about 

 3 days. In the other series one of the antigens 

 was detected in 4-day embryos but the other 

 three antigens did not appear until after 

 hatching. Yeas ('49) studied antigens of 

 sheep red cells, nine of which are detected 

 by use of immune sera and one (R) by 

 means of an isoagglutinin present in the 

 serum of certain sheep (not possessing the 

 R antigen). The former were found to be 

 present at birth, but the latter did not usually 

 appear tmtil two or three weeks later. While 

 the red cells of the newborn R lambs did not 

 possess the antigen, it was found to be pres- 

 ent in the serum of the animal at that stage 

 as well as in the adult. This antigen, then, 

 appears in the serum before it can be de- 

 tected in the red cells of the animals. It 

 would be of further interest to learn whether 

 or not the antigen is detectable in various 

 tissues of the fetus and early embryos. In the 

 chick Witebsky and Szepsenwol ('34) found 

 Forssman antigen to be present in, and 

 equally extractable from, first to twelfth day 

 embryos. In humans fetal hemoglobin is re- 

 ported to be antigenically different from that 

 of the adult (Darrow et al., '40). 



The extensive genetic studies that have 

 been made on the blood groups of man and 

 lower vertebrates have clearly established the 

 fact that these cellular antigens are gene- 

 determined. In fact the antigens seem to be 

 rather direct products of their causative 

 genes, each antigen being produced by the 

 action of a specific gene with no influence, 

 in general, of other genes or of the environ- 

 ment. Since all of the cells of an organism 

 are supposed to contain the full complement 

 of genes, the appearance of these antigens on 

 the surface of particular cells raises the 

 same sorts of questions as are involved in 

 the development of any particular gene- 

 determined character in particular tissues. 

 Certain antigens, such as the A and B char- 

 acters of humans, are found in most other 

 tissues of the body, whereas others, such as 

 the human M and N antigens, are restricted 

 to the blood cells. Thus, certain genes seem 

 to be active in a variety of tissues in im- 

 pressing a certain specificity on the tissue 

 substances, while others act to an appreciable 



