568 



Ontogeny of Immunological Properties 



later occurs between ectodermal and en- 

 todermal cells. At this time, too, initial in 

 vitro combinations of entodermal and ecto- 

 dermal cells fail to unite. However, meso- 

 dermal cells are found to be capable of 

 uniting with either of the others and are 

 thus capable of tying together cells of the 

 other two germ layers. The various inter- 

 actions occur only as a result of contact and 

 there is no indication of the operation of 

 forces acting at a distance. These and other 

 experiments of Holtfreter and of others serve 

 to emphasize the antigen-antibody analogy. 

 On this basis the specific adhesion or non- 

 adhesion of cells and tissues would depend 

 upon the extent of complementariness of 

 chemical structure of the respective cell 

 surfaces, and the changes that these undergo 

 during development. A similar point of view 

 has been developed in more detail by Weiss 

 ('41, '47). 



Through the auto-antibody concept this 

 can be related to genie action. It is known, 

 especially from the work on the antigens of 

 vertebrate blood cells, that the antigenic 

 composition of the cell surface is gene- 

 determined (see reviews by Irwin, '47, '49). 

 The antigens appear to be rather direct prod- 

 ucts of their causative genes, each of which 

 manifests itself independently of its allele. 

 Cells belonging to different tissues do not, 

 as a rule, possess the same set of surface 

 antigens despite the presumed identity of 

 chromosomal constitution of all the somatic 

 cells of the body. Certain antigens, such as 

 the A and B structures of himians, are found 

 on most other cells and tissvie fluids, whereas 

 other antigens, such as M, N, and Rh, are 

 restricted to the red blood cells. According to 

 the auto-antibody concept each gene would 

 serve as a mold or template upon which is 

 formed a complementary structure. This 

 may represent a terminal step or be merely 

 an intermediate step in a series of such 

 syntheses. The antigenic differences between 

 the surface of cells of different tissues can 

 be interpreted in various ways. The simplest, 

 perhaps, would be the assumption that all 

 of the genes are active, but at different rates 

 in different tissues, so that the surface in 

 each case would be composed of a different 

 assortment of the products of activity of the 

 genes. Each antigenic structure on the sur- 

 face of the cell may, then, be regarded as 

 representing a specific structural aspect of 

 the determining gene or the complement of 

 that structure. The extent to which the cells 

 of one tissue have surface substances that 

 are complementary to those of another tissue 



would determine the degree of association of 

 the two tissues. Within one tissue the ad- 

 hesion of the cells may be regarded as in- 

 volving combination of surface substance of 

 one cell with complementary subsurface 

 substance of another, in a manner previously 

 suggested (Tyler, '40) for auto-agglutination 

 phenomena. 



RELATION TO INDUCTION 



For the other aspect of the problem of 

 differentiation that we wish to consider, 

 namely the phenomenon of induction, there 

 is, as yet, only slight indication that the 

 antigen-antibody type of interaction may be 

 involved. One indication is that inductive 

 activity is associated more with protein 

 materials than with other types of extracts 

 of inductor tissue (see Holtfreter, '33, '48b; 

 Earth and Graff, '43). Inductive action re- 

 quires contact with the indvicing tissue and 

 it is evidently not dependent upon special 

 metabolic properties of the latter, since dead 

 tissues possess inductive capacity. This ca- 

 pacity may depend, then, upon the presence 

 of a specific type of protein, or other macro- 

 molecular substance, on the surface of the 

 natural inductor. The fact that certain tissues 

 which lack inductive action in the living 

 state acquire this capacity when killed may 

 be attributed to the exposure of inductor 

 substance, previously located in a svibsurface 

 position. 



For speculation along this line to acquire 

 any significance it would be important to 

 know whether specific morphological changes 

 can be brought about in cells by the action 

 of antibodies. It is, of course, well known 

 that cells of various types can be lysed by 

 treatment with immune antibodies in the 

 presence of complement. This, however, is 

 a lethal effect that would certainly not 

 warrant any consideration unless non-lethal 

 steps in the process were demonstrable. 

 There are two somewhat similar lines of 

 work that bear on this point. One is the 

 work with the so-called reticulo-endothelial 

 immune serum of Bogomolets (see reviews 

 by Pomerat, '45, '46; Straus, '46). This serum 

 is cytotoxic or inhibiting in high concentra- 

 tion. In low doses it has been claimed to 

 stimulate cellular growth and activity. How- 

 ever, careful in vitro tests of this by Pomerat 

 have not revealed any very marked stimula- 

 tory action. The other work consists in ex- 

 periments by Weiss ('47) in which hen's 

 eggs, at 60 hours to 8 days of incubation, 

 were injected with antisera prepared against 



