Alexander Wolsky

SEXUAL DIMORPHISM IN THE HISTOCOMPATIBILITY REACTIONS OF AMPHIBIA TO SKIN HOMOGRAFTS AND A TENTATIVE EXPLANATION OF THEIR MECHANISM

Recent experimental work (Eichwald et al., 1957; Billingham, 1958) has shown that in mammals there are histocompatibility factors evidently associated with the Y chromosome that are responsible for the tolerance or rejection of isografts by the host. It was shown that when isografts were made in certain mice considered genetically identical but differing only in sex, the grafts were sometimes rejected. This occurred, however, only when the donor was male and the host female. When the female was the donor and the male the host, no rejection was noted. Since the animals differed from each other only in sex, it has been supposed that the isografts were rejected or retained because of differences in an antibody response of the host to factors of the graft that existed only on the Y chromosome, that is, only in the male. These factors were called histocompatibility or histoincompatibility factors. Hauschka recently has noted (personal communication, 1958) that a crossover between the X and Y chromosomes may take place involving these factors so that in some instances females will have the factors. Work in our laboratory has indicated that a similar mechanism exists in the newt Triturus viridescens. In this animal, however, the factors are probably responsible for the rejection of skin homografts and not only for isograft rejection, as in mammals. Other evidence tends to indicate that the female also plays a role in the phenomena of homotransplantation. In the following a brief summary is given of experiments and their main results, the details of which will be published elsewhere (Pizzarello, 1960). This is followed by a discussion and a tentative explanation of the findings.

THE EFFECTS OF SPLEEN HOMOTRANSPLANTATION ON THE FATE OF SKIN HOMOGRAFTS IN TRITURUS VIRIDESCENS

Eichwald and Silmser (1955) drew attention to the characteristic phenomenon occurring in certain cases in skin grafts exchanged between individuals of the same strain of mice but of different sex. The two sexes behaved differently in skin homotransplantation, and this sexual dimorphism has been known since then as the Eichwald-Silmser effect. Pizzarello and Wolsky (1958), working on Triturus oiridescerrs, found that the Eichwald-Silmser effect, previously reported only in warm-blooded animals, is also present among cold-blooded vertebrates. However, slightly different sexual relationship was found in this case between skin homografts. Female skin was fairly well tolerated both by male and female hosts (grafts survived for a t least 2 months, or longer), whereas male skin was rejected promptly both by male and female hosts in 10 to 18 days. The results were almost diametrically reversed when not one but several (4 to 6, sometimes up to 10) skin patches of the same sex were transplanted simultaneously to one single host. In these multiple skin-graft experiments the female skin was promptly rejected and the male skin was tolerated, but only by the male hosts (Pizzarello and Wolsky, 1960). To account for these rather paradoxical results a temporary working hypothesis was constructed (Pizzarello and Wolsky, 1960 (page 51 and following)) which assumed that (1) the male tissues contain more (or more active) antigens than the females-presumably because of some histocompatibility genes on the Y chromosome, which do not exist (or exhibit a negative position effect) on the X chromosome; and (2) that female tissues react more vigorously to antigens with antibody elaboration than the male tissues, perhaps because of their XX constitution. With these assumptions one can explain the two single skin-graft categories (female-to-male and female-to-female) in which no graft rejection (or resorption) occurs, as being due to too little antigen activity; whereas the multiple-graft category without rejection (male-to-male) is assumed to be a consequence of the weak antibody-building capacity of the host being paralyzed, or overwhelmed by too much antigen. The present paper is the result of experiments designed to test the above tentative explanation, especially the latter assumption of an immunological paralysis due to an overdose of antigens in certain cases. It was known-and the present paper confirms this-that the rejection and resorption of an incompatible skin graft in the Triturus salamander is carried out by a cellular mechanism: lymphocytes, which attack in great numbers and literally eat away the incompatible foreign tissue (see Pizzarello and Wolsky, 1960 (FIGURE 2)). It was thought therefore that lymphocytes may also be the main source of antigens

AN ANALYSIS OF THE ACTINOMYCIN INDUCED CLEAVAGE DELAY IN SEA URCHIN EGGS.

Summary1.Arbacia punctulata eggs, treated with actinomycin D in a low concentration for 3 to 4 hours before fertilization, need about 40 per cent more time to complete the first cleavage than untreated controls.2.The delay is due to a slow movement and fusion of the pronuclei, the duration of the actual cleavage mitosis remaining unaffected.3.The phenomena can be formally explained by assuming that actinomycin interferes (through messenger RNA) with the synthesis of specific proteins, needed at fertilization, probably for the formation of the achromatic apparatus.