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12:24
Murine Model of CD40-activation of B cells
Published on: March 5, 2010
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In vitro Activation of B-CLL Cells
T Defrance1, A C Fluckiger1, J F Rossi2
1a Schering-Plough, Laboratory for Immunological Research, 27 Chemin des Peupliers, PO Box 11, 69571, Dardilly Cedex, France.
Leukemia & Lymphoma
|July 28, 2016
Summary
This study shows that B-cell chronic lymphocytic leukemia (B-CLL) cells can be stimulated to grow and differentiate using specific cytokine combinations. Interleukin-2 (IL-2) with anti-Ig reagents or Interleukin-4 (IL-4) with anti-CD40 antibodies can overcome maturation blocks in these leukemia cells.
Area of Science:
- Immunology
- Hematology
- Cell Biology
Background:
- B cells require surface molecules for activation and progression signals.
- CD40 antigen plays a crucial role in antigen-dependent B cell maturation.
- B-cell chronic lymphocytic leukemia (B-CLL) cells express CD40.
Purpose of the Study:
- To examine the capacity of purified B-CLL cells to be stimulated by cytokines for growth and differentiation.
- To investigate the effects of crosslinking surface Ig receptors or CD40 antigen on B-CLL cells.
- To determine the role of IL-2 and IL-4 in B-CLL proliferation and differentiation.
Main Methods:
- Purified B-CLL cells were stimulated with various cytokines after crosslinking of surface Ig (sIg) or CD40.
- Cell proliferation was assessed in response to different cytokine combinations.
- Immunoglobulin (IgM) synthesis and Ig isotype switching were analyzed.
Main Results:
- IL-2 was the primary cytokine inducing proliferation of anti-Ig activated B-CLL cells.
- IL-4 suppressed IL-2-driven proliferation in anti-Ig activated B-CLL cells but induced proliferation when CD40 was ligated.
- IL-4 and IL-2 showed additive effects on B-CLL growth upon CD40 ligation; IL-4 with anti-CD40 activated refractory leukemia specimens.
- Most B-CLL samples produced IgM upon SAC stimulation, potentiated by IL-2 and antagonized by IL-4.
- Anti-CD40 mAb alone or with cytokines did not induce Ig secretion or isotype switching.
Conclusions:
- B-CLL cells can be released from maturation arrest in vitro using IL-2/anti-Ig reagents or IL-4/anti-CD40 mAb.
- The differential effects of IL-4 on B-cell growth and differentiation depend on the activation signal used.
- Targeting CD40 with IL-4 may offer a therapeutic strategy for certain B-CLL cases.
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