The distribution of antibody-forming cells of different specificities in the lymph nodes and spleens of guinea pigs immunized with two separate antigens or with antigens bearing two determinants was studied. When animals were immunized with two soluble protein antigens or antigens in which the two antigenic determinants were on the same molecule, antibody-forming cells of different specificities were always randomly intermixed. However, when animals were immunized with two heat-aggregated particulate protein antigens and then boosted with soluble protein antigens, cells of different specificities were often seen to occur in groups.
These results suggest that antibody-forming cells may not arise by the antigen-stimulated proliferation of precommitted antibody-forming cells, but rather antibody-forming cells arise by a transformation of uncommitted precursor cells as the result of their interactions with a locally produced material derived from the processing of antigen.