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Cross-linking of membrane IgM on B CLL cells: dissociation between intracellular free Ca2+ mobilization and cell proliferation.
- Source :
-
European journal of immunology [Eur J Immunol] 1988 Nov; Vol. 18 (11), pp. 1811-7. - Publication Year :
- 1988
-
Abstract
- It has been shown previously that chronic lymphocytic leukemia (CLL) B cells are frozen at different stages of activation with unique requirements for proliferation. Although most B CLL cells express surface IgM, anti-mu antibodies are able to trigger only some of them to proliferate and/or respond to B cell growth factor (BCGF) or interleukin 2 (IL2), as normal B cells. In this report we extend these observations using three different monoclonal antibodies (mAb) to human mu chain (one mitogenic in soluble form for normal B cells, the two others mitogenic only when coupled on Sepharose 4B beads). Cells from only 3 out of 11 B CLL patients proliferated in the presence of either mitogenic anti-mu. When the early events following surface Ig cross-linking, such as calcium mobilization (by flow cytometry on indo-1-labeled cells), were studied all three mAb in soluble form were able to induce a similar increase in the intracellular free calcium concentration ([Ca2+]i); analogous to [Ca2+]i rise after the mitogenic F(ab')2 anti-mu stimulation. This response was seen only in 8 out of the 12 CLL B cells studied. All B CLL cells, however, proliferate in response to a combination of phorbol ester 12,13-dibutyrate (PBt2) and ionomycin. Therefore, three patterns of response to sIg cross-linking by anti-mu could be distinguished: cells from 4 out of 12 cases proliferate and mobilize Ca2+ upon anti-mu triggering (behaving like resting B lymphocytes); in 4 other cases anti-mu lead to Ca2+ mobilization without cell proliferation; in the last 4 cases neither Ca2+ mobilization, IP3 generation (in the one case studied) nor cell proliferation are observed although these cells do proliferate directly in response to growth factors. Moreover, anti-mu stimulation in this group leads to increased proliferation in response to BCGF and IL2 suggesting an anti-Ig signaling independent of inositol phosphate metabolism. These results are interpreted in terms of differential anti-mu signaling on B cells at different stages of activation.
- Subjects :
- Antibodies, Anti-Idiotypic immunology
Cross-Linking Reagents
Ethers pharmacology
Humans
Immunoglobulin mu-Chains physiology
Inositol Phosphates physiology
Interleukin-2 pharmacology
Interleukin-4
Interleukins pharmacology
Ionomycin
Phorbol Esters pharmacology
Tumor Cells, Cultured
B-Lymphocytes physiology
Calcium physiology
Cell Division
Leukemia, Lymphocytic, Chronic, B-Cell physiopathology
Receptors, Antigen, B-Cell physiology
Subjects
Details
- Language :
- English
- ISSN :
- 0014-2980
- Volume :
- 18
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- European journal of immunology
- Publication Type :
- Academic Journal
- Accession number :
- 3144454
- Full Text :
- https://doi.org/10.1002/eji.1830181124