CHARACTERIZATION OF THE MOLECULES ON SJL/J LYMPHOMAS WHICH STIMULATE SYNGENEIC T CELLS (IMMUNOLOGY, IA ANTIGENS, HISTOCOMPATIBILITY)

SJL/J mice have a high incidence of spontaneously arising lymphomas or reticulum cell sarcomas (RCS) which develop in aged mice. While transplantable RCS tumors grow well in normal SJL/J mice, they fail to grow in immunodeficient mice. In addition, these tumor cells stimulate marked syngeneic T cell proliferation. The results from inhibition studies using monoclonal antibodies demonstrated that SJL T cells proliferate in response to syngeneic I-A antigens, or to antigens closely associated with I-A on RCS cells. The nature of the RCS stimulatory antigen was futher examined using two different approaches. First, the specificity of T cells from semiallogeneic bone marrow chimeras was studied to determine how T cells are taught to recognize the stimulatory antigens on RCS cells. Second, these antigens were examined directly by isolating and characterizing the molecules on RCS cells which stimulate syngeneic T cells. SJL T cells appear to be taught to respond to RCS antigens in the thymus of "responder" mice, while T cells from "non-responder" F1 mice either never learn to respond, or are taught not to respond to these antigens. Complete I-E antigens, which are not present on normal SJL cells, are not expressed by RCS cells and are not involved in stimulating SJL T cells. Biochemical studies of I-A antigens isolated from RCS and normal SJL cells showed that RCS I-A antigens are structurally distinct from I-A antigens on normal SJL spleen, peritoneal exudate, and dendritic cells. Analysis of I-A antigens isolated from normal, tunicamycin, and neuraminidase treated cells suggests that RCS cells express highly glycosylated Aa chains on their surface which are not found on normal SJL spleen cells. However, SJL LPS blasts express acidic Aa chains which are similar to RCS Aa chains, and distinct from those expressed on SJL accessory cells. It is concluded that RCS cells express highly glycosylated I-A molecules which are particularly stimulatory to syngeneic T cells. The finding that normal activated B cells can express similar glycosylated I-A molecules suggests that RCS cells may represent a stage in B cell development at which B cells become highly stimulatory to syngeneic T cells.