Antigen shedding vs. development of natural suppressor cells as mechanism of tumor escape in mice bearing Ehrlich tumor.

C57BL/6J mice immunized with devitalized Ehrlich tumor (ET) cells produce high serum levels of IgM antibodies to ET cell-surface carbohydrates that are critical in the observed resistance against this tumor. However, this response is not found in ET-bearing mice at any stage of tumor development. Since previous studies had shown splenic natural suppressor (NS) cells in ET-bearers, their role in such IgM impairment was assessed. Here we show that tumor-bearers' spleen cells (TBSC) are unable to produce IgM in vitro in response to LPS, due to the presence of NS cells. Nevertheless, TBSC do produce IgM antibodies to ET cell-surface carbohydrates in increasing amounts as the tumor progresses. Yet these antibodies are not detected in sera of ET-bearers and are greatly decreased in immunized mice with a growing tumor. Moreover, increasing amounts of circulating carbohydrates, able to absorb most specific IgM, are found in ET-bearing sera associated with a large molecular size structure(s). These carbohydrates are also found in ET cell-culture supernatants and cell-free ascites fluid derived from this tumor, indicating their tumor origin. Taken together, our results indicate that lack of specific IgM antibodies in ET-bearing mice is not due to faulty production, but to in vivo absorption by carbohydrates shed from ET cells in increasing amounts as the tumor progresses. Thus, NS cells are unable to suppress this IgM production in vivo, despite the strong suppressor activity they show for many responses in vitro.