ABSTRACT
Despite the role of secreted immunoglobulin D (IgD) remains still largely unknown, previous studies have suggested that secreted IgD could induce basophils degranulation in some allergic asthma patients. In the present study we have searched direct evidence of the action of IgD on KU812 cells, generally classified as an immature basophilic cell line. We analyzed by flow cytometry the capacity of IgD, purified from IgD myeloma sera, to bind KU812 cells. Biotinylated monomeric IgD (mIgD) and biotinylated oligomeric IgD (oIgD) could bind KU812 cells. Blocking experiments with others immunoglobulin isotypes showed that KU812 cells expressed an unspecific receptor for IgD. However, oIgD but not mIgD enhances the release of interleukin-6 (IL-6) from KU812 cells. On the other hand, mIgD and oIgD failed to induce histamine release from KU812 cells or from cord blood derived basophils. Since IL-6 is known to induce basophil differentiation, we proposed that IgD could be implicated in allergic disorders by stimulating IL-6 release by prebasophil cells, then IL-6 could further induce an autocrine maturation of the cells.
Subject(s)
Basophils/metabolism , Flow Cytometry/methods , Immunoglobulin D/metabolism , Interleukin-6/metabolism , Leukemia, Basophilic, Acute/metabolism , Basophils/drug effects , Basophils/immunology , Cell Line, Tumor , Dose-Response Relationship, Drug , Humans , Immunoglobulin D/immunology , Immunoglobulin D/pharmacology , Leukemia, Basophilic, Acute/immunologyABSTRACT
The capacity of alpha-interferon (alpha-IFN) to induce lymphokine activated killer (LAK) cytotoxicity in the absence of interleukin-2 (IL2) has prompted us to test whether its ability to reduce dramatically the number of Ph1+ clones in chronic myelogenous leukemia (CML) patients is in part mediated through the generation of natural killer (NK) or LAK activity. The latter were tested using NK-sensitive (K562) and NK-resistant (Raji) cell lines in a target-cell colony-growth inhibition assay. Effector cells (E) were patient blood mononuclear cells (MC) without in vitro activation prior to their coculture with targets (T). Here we report that cytogenetic remission in alpha-IFN-treated patients is associated with significantly enhanced NK and LAK activities. Nevertheless, some patients under alpha-IFN therapy were found to develop lymphoid blast crisis despite high levels of NK and LAK activities, and partial or total cytogenetic remission. In contrast, most of the patients who developed nonlymphoid blast crisis presented 100% Ph1+ cells and displayed defective NK and/or LAK activity. These observations could favor the hypothesis that there is an indirect but complex effect of alpha-IFN on leukemic cells, mediated by cells involved in immune surveillance; and also that lymphoid blast cells may actually escape LAK cytotoxicity.
