REQUIREMENT FOR INCREASED IL-10 IN THE DEVELOPMENT OF B-1 LYMPHOPROLIFERATIVE DISEASE IN A MURINE MODEL OF CLL

Malignant B-l cells derived from NZB mice, a murine model of spontaneo us autoimmunity and B cell lymphoproliferative disease, produce signif icantly higher levels of IL-10 mRNA than normal B-l or B cells, IL-10 may act as an autocrine growth factor for the expansion of malignant B -l cells. In order to determine if elevated endogenous production of I L-10 was a required element for the malignant transformation of B-l ce lls in NZB mice, backcross animals were studied for the linkage betwee n elevated IL-10 expression and the presence of lymphoid malignancy. T he phenotypes of aged (NZB x DBA/2)F-1 x NZB animals were determined a nd a strong correlation was found between the elevated levels of IL-10 mRNA and the development of B-l malignant clones, In contrast, an inc reased level of IL-10 message was not associated with elevated serum I gM or the presence of anemia or reticulocytosis which is mainly seen i n response to autoantibody production. These results indicate that, at least in NZB, the autoimmunity and lymphoproliferation phenotypes are not linked genetically, IL-10 may enhance proliferation and the devel opment of B-l cell malignancy rather than antibody production by the B -l cell subpopulation, Thus, IL-10 plays an important role in B-l mali gnancies, and downregulation of IL-10 could be a likely site for inter vention in B cell malignancies.