Responsiveness of Chronic Lymphocytic Leukemia B Cells Activated Via Surface Igs or CD40 to B-Cell Tropic Factors

• Published in: Blood 1992-12, Vol.80 (12), p.3173-3181
• Main Authors: Fluckiger, A.C., Rossi, J.F., Bussel, A., Bryon, P., Banchereau, J., Defrance, T.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal - pharmacology; Antigens, CD - analysis; Antigens, CD - immunology; Antigens, Differentiation, B-Lymphocyte - immunology; B-Lymphocytes - drug effects; B-Lymphocytes - immunology; Biological and medical sciences; CD40 Antigens; Cell Cycle - drug effects; Cells, Cultured; Cytokines - pharmacology; Female; Growth Substances - pharmacology; Hematologic and hematopoietic diseases; Humans; Immunophenotyping; Interleukin-2 - pharmacology; Interleukin-4 - pharmacology; Kinetics; Leukemia, Lymphocytic, Chronic, B-Cell - immunology; Leukemia, Lymphocytic, Chronic, B-Cell - pathology; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymphocyte Activation - drug effects; Male; Medical sciences; Middle Aged; Neoplasm Staging; Receptors, Antigen, B-Cell - immunology; Recombinant Proteins - pharmacology
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V80.12.3173.3173

Recent studies performed in the laboratory have established that interleukin-4 (IL-4) used in combination with anti-CD40 monoclonal antibody (MoAb) 89 presented on Ltk– mouse fibroblasts stably expressing human F$$RII/CDw32 (referred to as the CD40 system) sustains long-term proliferation of normal human B cells. In the present study, B-cell chronic lymphocytic leukemias (B-CLLs) activated through slgs or CD40 were examined for their capacity to proliferate and differentiate in response to various cytokines. Our results indicate that the outcome of IL-4 stimulation on the in vitro growth of B-CLL depends on the signalling pathway used for their activation. Whereas IL-4 did not display any growth-stimulatory effect on B-CLL activated by Ig cross-linking agents, it could stimulate DNA synthesis and enhance the viable cell recovery when leukemic B cells were cultured in the CD40 system. Most B-CLL samples were induced for IgM synthesis upon Staphylococcus aureus strain Cowan I stimulation. This Ig response was potentiated by IL-2 and antagonized by IL-4. Anti-CD40 MoAb used alone or in combination with cytokines (IL-1α to IL-6, interferon $$, tumor necrosis factor y, and transforming growth factor B) failed to induce Ig secretion from B-CLL cells. No evidence for Ig isotype switching was obtained with the cytokines listed above, regardless of the mode of activation. Taken together, our results suggest that B-CLL cells can be partially released from their apparent maturation block by IL-2 and Ig cross-linking agents. In contrast, combinations of IL-4 and cross-linked anti-CD40 antibodies induced entry of B-CLL cell into cycle, but poorly stimulated their differentiation into Ig secreting cells. © 1992 by The American Society of Hematology.