MECHANISM OF ANTIBODY FORMATION 67 



in human subjects markedly hypersensitive to horse serum, scarlet fever 

 antitoxin when administered locally, loses its neutralizing effect for 

 specific toxin more quickly than it does in non-sensitive persons. 



The above cited observations shov^ that in the presence of an 

 insufficient amount of antibody production the antigen persists in the 

 host and continues to exercise an effect until completely destroyed by 

 the host enzymes. When an adequate amount of antibody is produced 

 it may completely block the activity of an antigen. In an ordinary 

 immunization experiment these conditions might correspond to the 

 stage v^'hen the peak of antibody titer is reached, which then is followed 

 by an abrupt decline of antibody production for the above stated 

 reasons. 



B. THEORIES ON THE SITE OF ANTIBODY FORMATION 



1. The Lymphocytic Theory 



For over 40 years statements bearing on the lymphocytes as the 

 site of antibody formation have been made by various investigators. 

 Pfeiffer and Mark (1898) reported that anti-cholera antibodies ap- 

 peared in the spleen, bone marrow, and lymph nodes before any in- 

 crease could be detected in the blood. Anti-rabbit red cell hemolysins 

 were reported to be present in serum, lymph from the thoracic duct, 

 neck lymph, lymph from the limbs, salivary glands, etc. (Hughes and 

 Carlson, 1908). Intravenous injection of antisera was followed by con- 

 centrations of antibodies in thoracic duct lymph greater than in 

 cervical lymph (Becht and Luckhardt, 1916). Takahashi (1933) 

 reported finding in the lymph of the rabbit anti-human red cell ag- 

 glutinins flowing from lymph nodes, and believed that agglutinins were 

 manufactured there. (For further detailed discussion see Drinker and 

 Yoffey, 1941; Dougherty and White, 1947.) McMaster and Hudock 

 (1935) summarizing numerous reasons, concluded that agglutinins are 

 formed in the lymph nodes; and McMaster and Kidd (1937) observed 

 the antiviral principle in the regional lymph nodes of rabbits which 

 were injected with vaccinia in the ears. 



Intensive studies on this question have since been carried out by 

 Ehrich and Harris at the University of Pennsylvania, Dougherty, 

 White and Chase at Yale University and Burnet and his co-workers in 



