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Related Concept Videos

B Cell Activation and Differentiation01:24

B Cell Activation and Differentiation

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The adaptive immune response, a sophisticated defense mechanism, relies on the activation and differentiation of B lymphocytes, or B cells. These processes enable our bodies to mount a tailored response against specific pathogens such as bacteria, free virus particles, toxins, and parasites.
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Murine Model of CD40-activation of B cells
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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
PubMed
Summary
This summary is machine-generated.

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.

Keywords:
IL-2IL-4In vitro activation of B-CLLcytokines in CLL

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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.