Cellular sites of formation of gamma globulin.

The cellular sites of formation of gammaglobulin in lymphatic tissues of man and in a representative human lymphoid infiltrate have been studied by fluorescent antibody technique. The findings indicate that gamma-globulin is formed in the germinal centers of lymphatic nodules and in the cytoplasm of mature and immature plasma cells of two types-those with and those without Russell bodies. The germinal center cells that synthesize gamma-globulin have been designated "intrinsic" cells to distinguish them from the medium and large lymphocytes, and the primitive reticular cells that occur elsewhere and do not produce gamma-globulin. Unlike the plasma cells, which function as individual units, the intrinsic cells apparently form gamma-globulin only when they are arranged in discrete aggregations. The function, the blood supply, and the systematic cellular arrangement of germinal centers justifies the postulate that they are miniature organs of internal secretion of gamma-globulin. The release of gamma-globulin from its sites of formation appears to be accomplished by holocrine and apocrine secretion. Presumably, these secretory mechanisms are adaptations required for the production of antibody since they have not been described in parenchymal cells that form the other serum proteins. The cells found to form gamma-globulin appear to be identical with those previously shown to form specific antibody in response to a variety of antigens in the experimental animal. This evidence indicates that normal gamma-globulin, if it exists, originates in the same cells that produce antibody. It is suggested, also, that each of the 3 morphologically distinct categories of cells that synthesize gamma-globulin represents a response to a particular form of antigenic stimulation. Nuclear participation in the process of gamma-globulin synthesis was not detected by the technique employed.