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

Immunologic differences among the chronic B lymphoid leukemias defined by the French-American-British (FAB) classification were evaluated with respect to IgE isotype switching induced by anti-CD40 monoclonal antibody (mAb) and cytokines.We immunocytochemically studied IgE isotype switching of leukemic B cells from 25 cases and three cell lines established from the leukemias after stimulation with anti-CD40 mAb, plus each of the following cytokines: interleukin 2 (IL-2); IL-4; IL-10; tumor necrosis factor alpha (TNF-alpha); and transforming growth factor beta (TGF-beta). Also, genomic Cepsilon and Cepsilon transcripts were analyzed by polymerase chain reaction and reverse transcriptase polymerase chain reaction.Leukemic cells from hairy cell leukemia variant and its cell line, with deletion of the Cepsilon gene, did not undergo IgE isotype switching in response to any of the stimuli. In contrast, a cell line (FH-5) established from chronic lymphocytic leukemia cells, bearing the Cepsilon gene, underwent the highest level of IgE isotype switching on stimulation with anti-CD40 mAb and IL-4. This response was correlated with the production of Cepsilon transcripts. IL-4, IL-10, and TNF-alpha induced higher levels of IgE isotype switching than the others. No IgE isotype switching was observed in any of the non-Hodgkin's lymphomas examined, except mantle cell lymphoma and lymphoplasmacytic lymphoma. Percentages of CD40(+) cells in five cases with follicular lymphoma were significantly lower than the other leukemias.IgE isotype switching induced by anti-CD40 mAb with cytokines other than IL-4 was first demonstrated, whereas none of the non-Hodgkin's lymphomas except mantle cell lymphoma and lymphoplasmacytic lymphoma showed IgE isotype switching in response to any of the stimuli. Cells of follicular lymphoma were suggested to be different from cells of the other leukemias.