Differences in IgE isotype switching induced by anti-CD40 monoclonal antibody and cytokines among subtypes of chronic B lymphoid leukemias

Objective. Immunologic differences among the chronic B lymphoid leukemias d efined by the French-American-British (FAB) classification were evaluated w ith respect to IgE isotype switching induced by anti-CD40 monoclonal antibo dy (mAb) and cytokines. Materials and Methods, We immunocytochemically studied IgE isotype switchin g of Leukemic B cells from 25 cases and three cell lines established from t he Leukemias after stimulation with anti-CD40 mAb, plus each of the followi ng cytokines: interleukin 2 (IL-2); IL-4; IL-IO; tumor necrosis factor alph a (TNF-alpha); and transforming growth factor beta (TGF-beta), Also, genomi c C epsilon and CE transcripts were analyzed by polymerase chain reaction a nd reverse transcriptase polymerase chain reaction. Results. Leukemic cells from hairy cell leukemia variant and its cell line, with deletion of the CE gene, did not undergo IgE isotype switching in res ponse to any of the stimuli. In contrast, a cell line (FH-5) established fr om chronic lymphocytic leukemia cells, bearing the CE gene, underwent the h ighest level of IgE isotype switching on stimulation with anti-CD40 mAb and IL-4, This response was correlated with the production of Ca transcripts. IL-4, IL-10, and TNF-alpha induced higher levels of IgE isotype switching t han the others. No IgE isotype switching was observed in any of the non-Hod gkin's lymphomas examined, except mantle cell lymphoma and lymphoplasmacyti c lymphoma. Percentages of CD40(+) cells in five cases with follicular lymp homa were significantly lower than the other leukemias. Conclusions. IgE isotype switching induced by anti-CD40 mAb with cytokines other than IL-4 was first demonstrated, whereas none of the non-Hodgkin's l ymphomas except mantle cell lymphoma and lymphoplasmacytic lymphoma showed IgE isotype switching in response to any of the stimuli. Cells of follicula r lymphoma were suggested to be different from cells of the other leukemias . (C) 2000 International Society for Experimental Hematology. Published by Elsevier Science Inc.