MECHANISM OF ANTIBODY FORMATION 75 



"spoke" arrangement of the chromatin of the nucleus, or merely a 

 suggestion of this feature. Many of these cells correspond to the 

 concept of "plasma cellular reticulum cells" which are taken to be the 

 progenitors of plasma cells. Based on such careful analysis of various 

 factors, they concluded that there is constant direct proportionality 

 between the concentration of antibody formed and the degree of 

 plasma cell proliferation in the organism which has been immunized. 



Weighing various facts, one against the other, their reasonable ex- 

 planation is that plasma cell proliferation essentially originates from 

 elements of the reticulo-endothelial system, and as this system con- 

 stitutes quite a considerable part of the spleen, the splenic weight is 

 naturally increased by the proliferation in the reticulo-endothelial 

 system. In other organs, for instance, the liver, the relative weight of 

 the reticulo-endothelial system is too slight to influence noticeably the 

 weight of the organ during the process of immunization. 



Studying the cellular reaction in the rabbit spleen during the 

 secondary response, after intravenous reinjections of antigens, espe- 

 cially living bacteria, Fagraeus (1948) observed a very strong plasma 

 cellular reaction which was confined almost exclusively to the red pulp. 

 The antigen (^Salmonella typhi) was found in the periphery of the 

 lymph follicles and in the red pulp, while but little antigen could be 

 distinguished in the follicles. The great development of the plasma 

 cells in the red pulp of the spleen after the injection of the antigen was 

 thus preceded by the concentration of bacteria there. Successive stages 

 of the above-mentioned intense plasma cellular reaction, associated 

 with antibody formation, was accompanied by the finding of large 

 reticulum cells or transitional cells followed 1 to 2 days later by im- 

 mature plasma cells and, a few days later, an increase in the number 

 of plasma cells. The plasma cells were usually not detected in the 

 lymph follicles. In tissue culture studies, suggestive evidence of the 

 production of antibody by spleen tissue was obtained. The antibody 

 thus produced was from 20 to 200-fold in excess of the amount of 

 antibody he could obtain in tissue extracts made from pieces of tissue 

 from the parent spleen. Excised pieces of red pulp and lymph follicles, 

 abundant, respectively, in plasma cells and lymphocytes, were sepa- 

 rately studied for their capacities to form antibody. The antibody 

 production by red pulp cultures was considerably greater than that by 

 lymph follicle cultures. The production of antibody by the former 



