302 GEO. A. THIEL AND HAL DOWNEY 



taken place. The nucleus has begun to enlarge, and the chroma- 

 tin which was quite uniformly distributed, is collected in larger 

 knots. Part of the fine chromatic network still remains. In C 

 the nucleus has become very chai-acteristic; its nucleolus is a dis- 

 tinct structure, located in or near the center of the nucleus and 

 surrounded by a clear zone that contains but little chromatin. 

 The chromatin knots that were beginning to appear in B are 

 more numerous and are for the most part confined to the periph- 

 ery of the nucleus. The cell body is strongly basophilic. A cell 

 of this type continues to differentiate until it becomes the large 

 lymphocyte that is found in all the lymphoid tissue. 



These large lymphocytes show a marked proliferative activity 

 in a 4-cm. pig, their products being added to the groups of large 

 free cells that are found in the meshes of the splenic mesenchyme. 

 In a 6-cm. pig the process is more pronounced, many of the cells 

 having already differentiated into erythrocytes. 



The details of the modifications that take place in the stem- 

 cells as they develop into erythrocytes need not be reviewed here, 

 as many detailed accounts are found in the hematological litera- 

 ture. 



It should, however, be noted that the differentiating cells may 

 show considerable variation in size. The large lymphocytes may 

 undergo direct differentiation, or various cell divisions may inter- 

 vene, producing smaller cells which then take on the erythro- 

 blastic characters. In the first case the large cells still retain the 

 nuclear structure of the large lymphocyte when they already 

 show the presence of hemoglobin in their cytoplasm. The nu- 

 cleus later becomes dense and pycnotic, as seen in the typical 

 normoblast. In the second case, differentiation begins in a 

 smaller cell and the nuclear changes precede those of the cyto- 

 plasm. 



We are now confronted with the following problem: Is the 

 erythropoietic activity confined entirely to cells derived from the 

 local mesenchyme, or do erythroblasts brought in by the blood- 

 stream continue their multiplication and differentiation w^ithin 

 the meshes of the splenic tissue? After making a survey of a 

 number of 3- to 4-cm. embryos it was found that groups of blood- 



