Natural antibodies carrying a cross-reactive idiotype enhance tumor growth in the rat.

A population of Fab fragments was identified in the papain-solubilized fraction of membranes of a rat chemically-induced sarcoma, KMT 17. The Fab fragments were partially purified by gel filtration and column electrophoresis. A rabbit antiserum against the partially purified Fab fragments was raised and shown to be specific for Fab fragments by immunoelectrophoresis. Furthermore, four lines of evidence indicated that the KMT 17 Fab fragments carry a cross-reactive idiotype: (1) the antiserum could bind only with a restricted population of normal Fab fragments having a pl of 6.3; (2) an unrelated antibody (WKA anti-SRBC) showed a weak cross-reactivity (less than 6%); (3) syngeneic antisera against the KMT 17 could bind with the 125I-KMT 17 Fab preparation that was purified by an immunoabsorbent column with the rabbit anti-KMT 17 Fab antiserum (anti-idiotype antibody); (4) the rabbit anti-KMT 17 Fab antiserum could bind with neither heavy nor light chains of WKA IgG. The natural antibody carrying the idiotype was found in normal serum and in various organs as well, especially in the lung of the conventional rats. In addition, the fractions containing Fab fragments (Frll) were shown to enhance tumor growth when injected into syngeneic animals, whereas Fab-free fractions that were separated from the Fab fragments by column electrophoresis showed no enhancing activity. These results strongly suggested that a population of Fab fragments carrying a cross-reactive idiotype was responsible for the enhancement of tumor growth. Mechanisms for the biological function of natural anti-tumor antibodies carrying a cross-reactive idiotype are discussed.