LOW-GRADE B-CELL LYMPHOMAS OF MUCOSA-ASSOCIATED LYMPHOID-TISSUE (MALT-TYPE) REQUIRE CD4O-MEDIATED SIGNALING AND TH2-TYPE CYTOKINES FOR IN-VITRO GROWTH AND DIFFERENTIATION

To investigate the mechanisms of T cell dependence underlying the deve lopment of extranodal mucosa-associated lymphoid tissue (MALT)-type B cell lymphomas, the activation, proliferation, and differentiation of lymphoma B cells were studied using ligand binding to the CD40 membran e receptor. The activation and proliferative response of all investiga ted low-grade MALT-type lymphomas (n = 6) was strongly dependent on an ti-CD40-mediated signals and was complemented by cytokines produced by T helper cells of the Th2 type (interleukin-4 (IL-4) and/or IL-10). T h1 cytokines (IL-2 and/or interferon-gamma) hand little effect. Low-gr ade, but less so high-grade, MALT-type lymphoma B cells were induced t o secrete large amounts of tumor immunoglobulin in response to IL-10. In contrast, high-grade MALT-type lymphomas (n = 5) proliferated in re sponse to both Th2- and Th1-type cytokines and CD40 stimulation with o r without cytokines. These results suggest that CD40 signaling in comb ination with Th2 cytokines are essential for the development and progr ession of low-grade MALT-type B cell lymphoma. We conclude that T cell s, which activate B cells in a CD40-dependent fashion, may contribute to lymphoma pathogenesis.