260 HILDEMANN, LINSCOTT AND MORLINO 



or macrophages, evidence that they can differentiate into any 

 other cell type is unconvincing (Trov^ell, 1958). Our present 

 results with small lymphocytes are most readily accommodated 

 to the older view that an immunologically reactive cell is capable 

 of coping with diverse antigens. To maintain a clonal selection 

 view of the immune function of small lymphocytes, one must 

 argue that numerous cells of each relevant clone are present in the 

 initial inoculum and respond directly to antigenic stimulation 

 without need for replication of specifically competent cells. 

 However, mitotically active lymphoid cells would participate in 

 immune responses under normal conditions, and such cells are 

 required to account for anamnestic responses in general. In the 

 light of increasing evidence for the existence of lymphocyte- 

 associated cellular immunity as distinct from antibody globulin 

 production (Snell, Winn and Kandutsch, 1961), we are inclined 

 not to regard the capacity to elaborate humoral antibodies as an 

 essential criterion of immune reactivity at the cellular level (see 

 Burnet, 1959). Whether small lymphocytes are capable of dual 

 immune responses is not yet clear. 



A recent study of the order of appearance of blood cells in 

 newly hatched and young bullfrog larvae (Hildemann and Haas, 

 1962) indicates that all types of defmitive leucocytes other than 

 small lymphocytes appear during the period when larvae can still 

 be made completely tolerant to homografts. Small lymphocytes 

 were observed to appear and increase about ten-fold in number 

 during the time of transition from the homograft tolerance to 

 immune type of response at 40-50 days post-hatching. In other 

 vertebrates, including man, small blood lymphocytes first appear 

 in late embryonic or early postnatal life. Thus the apparent 

 relationship between the ontogeny of the lymphocytic system and 

 the maturation of the isoimmune response capacity provides 

 additional evidence that small (mature) lymphocytes play an 

 important role in transplantation immunity. 



Tyler (i960) has lately proposed that spontaneous cancer arises 



