SummaryB chronic lymphocytic leukemia (B-CLL) is characterized by the accumulation of slow-dividing and long-lived monoclonal B cells arrested at the intermediate stage of their differentiation . We previously showed that interleukin 4 (IL4) not only inhibits but also prevents the proliferation of B-CLL cells. We report here that IL-4 protects the B-CLL cells from death by apoptosis (programmed cell death [PCD]) . IL-4 inhibits spontaneous and hydrocortisone (HC)-induced PCD of highly purified B cells from 12 unselected CLL patients, as shown by sustained cell viability and lack of DNA fragmentation . IL1, -2, -3, -5, -6, -7, tumor necrosis factor a, and transforming growth factor (3 have no protective effect . The in vitro rescue from apoptosis by IL-4 is reflected by an increased expression of Bcl-2 protein, a proto-oncogene directly involved in the prolongation of cell survival in vivo and in vitro. Hence, IL-4-treated B-CLL cells express significantly more Bcl-2 than unstimulated, HC-treated, or fresh B-CLL cells. Furthermore, subcutaneous injection of IL4 into one CLL patient enhances Bcl-2 protein expression in the leukemic B cells . These data may suggest that IL-4 prevents apoptosis of B-CLL cells using a Bcl-2-dependent pathway. Given our recent observations that fresh T cells from B-CLL patients express IL-4 mRNA, we propose that IL-4 has an essential role in the pathogenesis of CLL disease, by preventing both the death and the proliferation of the malignant B cells .
In spite of intensive investigations, the ability of breast feeding to delay and to attenuate atopic diseases in children remains debatable. This study documents a mechanism whereby breast feeding might interfere with the synthesis of IgE by breast-fed infants. Indeed, we show that colostrum contains IgE-binding factors (IgE-BF) capable of suppressing the in vitro synthesis of human IgE. Colostrum obtained from 15 donors was successively depleted of lipids and casein, filtered through Amicon XM50 membrane (mol. mass cut-off 50 kDa) and lyophilized. IgE-BF was demonstrated in such preparations by two different approaches, i.e. a classical rosette inhibition assay and Western blot analysis. In the first instance, lyophilized preparations of colostrum inhibited the binding of IgE-coated bovine erythrocytes to IgE recovered on the surface of RPMI 8866 lymphoblastoid cells. The rosette-inhibiting activity could be absorbed on IgE- but not on IgG-Sepharose 4B and it could be recovered in the eluate of IgE-Sepharose 4B. The molecular mass of IgE-BF was comprised between 10 to 20 kDa as estimated by gel filtration through a calibrated Sephadex G-75 column. After fractionation on 12% sodium dodecyl sulfate-polyacrylamide gel electrophoresis and transfer to nitrocellulose membrane, colostrum displayed one band of 14 kDa and reacted with radiolabeled IgE but not with IgG nor IgM. This 14-kDa band could be removed by absorbing colostrum with IgE- but not with IgG-Sepharose 4B. Most importantly, the colostrum IgE-BF suppressed the spontaneous in vitro synthesis of IgE by B lymphocytes derived from allergic donors without altering the production of IgM.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.