Responsiveness of chronic lymphocytic leukemia B cells activated via surface Igs or CD40 to B-cell tropic factors
| Autor: | P Bryon, Jacques Banchereau, Thierry Defrance, A Bussel, JF Rossi, Anne-Catherine Fluckiger |
|---|---|
| Rok vydání: | 1992 |
| Předmět: |
Adult
Male medicine.drug_class Immunology Receptors Antigen B-Cell Biology Lymphocyte Activation Monoclonal antibody Biochemistry Immunophenotyping Antigens CD medicine Humans Interferon gamma CD40 Antigens Growth Substances Cells Cultured B cell Aged Neoplasm Staging Aged 80 and over B-Lymphocytes CD40 Cell Cycle Antibodies Monoclonal Cell Biology Hematology Transforming growth factor beta Middle Aged Leukemia Lymphocytic Chronic B-Cell Molecular biology Recombinant Proteins Antigens Differentiation B-Lymphocyte Kinetics medicine.anatomical_structure Immunoglobulin class switching biology.protein Cytokines Interleukin-2 Female Tumor necrosis factor alpha Interleukin-4 Antibody medicine.drug |
| Zdroj: | Europe PubMed Central |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood.v80.12.3173.3173 |
| Popis: | 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 Fc gamma 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-1 alpha to IL-6, interferon gamma, tumor necrosis factor gamma, and transforming growth factor beta) 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. |
| Databáze: | OpenAIRE |
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