HISTOLOGICAL CHANGES AFTER IRRADIATION 1103 



This destruction of lymphocytes is soon reflected in a drop in the number 

 of lymphocytes in the peripheral blood (Chap. 16 by Jacobson). 



After the administration of 800 r of total-body X radiation to rabbits, 

 nuclear debris of lymphocytes in the lymph nodes rises from an appreci- 

 able amount at Yi hour to a maximum at 8 hours (De Bruyn, 1948). It 

 is usually concentrated in the more active portions of the nodules rather 

 than at their periphery. Outside the nodules it is diffusely distributed 

 throughout cortex and medulla, sometimes with a little in the lumen of 

 small lymphatic vessels. The reticular cells show no evidence of damage. 

 Prompt phagocytic activity of macrophages results in almost complete 

 disappearance of debris by 24 hours, leaving large areas of lymphocyte- 

 poor tissue frequently characterized by dense masses of spindle-shaped 

 reticular cells. The concentration of these cells is probably due to a 

 collapse of the stroma rather than to a hyperplasia of the reticular cells, 

 since none of them are in mitosis. Medium-sized and large lymphocytes 

 frequently exhibit signs of damage, such as clumping of chromatin, loba- 

 tion of nuclei, or formation of giant cells, and many, but not all of them, 

 degenerate. As in the bone marrow, reticular cells and macrophages are 

 not visibly affected at any stage and are the main potential source of 

 regeneration of lymphocytes. Heterophil leukocytes appear in great 

 numbers during the first day and persist for several days, after which they 

 degenerate and are phagocytosed by macrophages. Edema of the con- 

 nective tissue about some of the nodes is prominent as late as 10 days 

 after irradiation. Following the disintegration and removal of the 

 lymphocytes, most of the lymphatic nodules disappear, leaving a promi- 

 nent reticular stroma for several weeks. 



Early regeneration is diffuse, nodular regeneration occurring much 

 later. Beginning at 5 days, diffuse areas of medium-sized lymphocytes, 

 many in mitosis, appear in the cortex and to some extent in the medulla. 

 Then, three weeks after irradiation, these cells begin to concentrate in 

 localized areas of the cortex, forming small "bare" germinal centers, 

 frequently associated with small areas of ectopic myelopoiesis. These 

 bare nodules gradually grow larger, develop a shell of small lymphocytes, 

 and by four months resume the appearance of typical nodules. Plasma 

 cells, noted from 9 days on, especially in the medullary cords, gradually 

 diminish after 36 days. 



In the lymph node, as in the bone marrow of animals exposed to X rays 

 (100 to 800 r), the damage is correlated with the amount of radiation. 

 This correlation holds, not only for the quantity of cellular debris, but 

 also for the alterations in the nodules. In contrast to complete destruc- 

 tion and delayed regeneration of a majority of the nodules in rabbit 

 lymph nodes after 800 or 600 r of X rays, after 400 r there is only partial 

 destruction and a greatly accelerated recovery, and after still lower doses 

 the changes are correspondingly less marked. After 100 and 50 r there is 



