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 .

This study indicates that hydrocortisone (HC) Clin. Invest. 1991. 87:870-877.)

No abstract

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.