Negative signaling in B cells by surface immunoglobulins
M Mayumi1, S Sumimoto, S Kanazashi
1Department of Pediatrics, Faculty of Medicine, Kyoto University, Japan.
The Journal of Allergy and Clinical Immunology
|December 1, 1996
Summary
Surface immunoglobulin cross-linking triggers B-cell death signals, but rescue signals can prevent this. Different cross-linking intensities lead to varied B-cell responses, impacting potential therapies for allergic disorders.
Area of Science:
- Immunology
- Cell Biology
- Molecular Signaling
Background:
- Surface immunoglobulins (Ig) on B cells transmit signals that can lead to cell death.
- Surface IgM is a primary transducer of these negative signals, with IgD and IgG also potentially involved.
- Rescue signals are necessary to prevent B-cell death induced by immunoglobulin cross-linking.
Purpose of the Study:
- To investigate the differential signaling consequences of surface IgM cross-linking in human malignant B lymphoma cell lines and normal B cells.
- To explore the role of rescue signals, including interferons and CD40 stimulation, in modulating B-cell responses to IgM cross-linking.
- To understand how varying intensities of IgM cross-linking influence B-cell fate, potentially informing therapies for allergic disorders.
Main Methods:
- Cross-linking of surface IgM on B lymphoma cell lines (B104, DND-39) and normal B cells using anti-IgM antibodies.
- Treatment with alpha- and beta-interferons, anti-CD40 antibody, and IL-4 to assess rescue signaling.
- Morphological analysis (necrosis vs. apoptosis) and assessment of cell adhesion molecules (CD11a/CD54).
Main Results:
- Anti-IgM antibody-induced B-cell death was differentially inhibited by interferons or anti-CD40 antibody in the two cell lines.
- B104 cells exhibited necrosis, while DND-39 cells showed apoptosis following anti-IgM stimulation.
- CD40 signaling and CD11a/CD54-dependent cell adhesion were involved in inhibiting negative signaling and mediating rescue in DND-39 cells and normal B cells.
Conclusions:
- Quantitative differences in surface IgM cross-linking intensity can elicit distinct signaling outcomes, ranging from DNA synthesis to apoptotic cell death.
- CD40-transduced signals can inhibit IgM-induced negative signaling, with cell adhesion playing a role in this rescue mechanism.
- Understanding these signaling pathways may lead to novel therapeutic strategies for allergic disorders by modulating immunoglobulin production.
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