358 PAUL S. RUSSELL 



disease. Distinct Malpighian corpuscles are rare on microscopic 

 examination as the normal splenic architecture gives way to a 

 population of large pale histiocytes in varying abundance, as 

 described by Gorer and Boyse (1959^), following injection of 

 parental cells into F^ hybrids (Figs. 5 and 6). 



The lymph nodes are smaller than normal and in the later 

 stages of the disease are barely identifiable on gross examination. 

 These tiny structures are firm in consistency and may show 

 considerable deposition of amorphous hyaline-like material and 

 a varying degree of infiltration by histiocytes (Fig. 7). Where 

 these destructive changes are less marked the lymphoid cells 

 show no apparent organization, merely lying in diffuse sheets. 

 Occasionally infiltrations of leucocytes, predominantly lymphoid 

 cells but also polymorphonuclear cells, are seen in the subcapsular 

 zone of the kidney. No cellular infiltrations have been found in 

 the intestinal wall, lung, muscle, skin or brain. The bone marrow 

 and thymus have not been systematically examined but the 

 impression from a few bone marrow specimens is that the 

 granulocytic series of cells predominates abnormally. 



(2) Dosage and route of injection oj spleen cells. Whereas the 

 intravenous administration of 5 iTiillion or more DBA/i spleen 

 cells to C57BL/6 newborns will cause the prompt death of about 

 96 per cent of the recipients, reducing the dose below this level 

 will still regularly result in a high percentage of runts although 

 the animals appear to grow to a slightly greater size and to 

 succumb, on the average, a few days later (Fig. 8). Our present 

 experience, considerably larger than at the time of the previous 

 preliminary report (i960), indicates that at doses smaller than 

 500,000 cells the incidence of runt disease declines sharply but that 

 smaller doses may occasionally produce all the changes typical of 

 runt disease. The smallest number of spleen cells capable of 

 producing the disease has not been accurately fixed and may, of 

 course, be a somewhat variable figure depending upon the relative 

 cellular constitution of the donor spleen at the time the animal is 



