Tumor necrosis factor-α and CD40L modulate cell surface morphology and induce aggregation in Ramos Burkitt's lymphoma cells

Reuven Laskov, Nir Berger, Matthew D. Scharff, Marshall S. Horwitz

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Interaction of CD40L and its cognate receptor is an essential component of B-lymphocyte signaling, affecting various aspects of B-cell differentiation pathways and immunoglobulin gene expression. However, much less is known about the biological consequences of B-cell signaling through tumor necrosis factor (TNF)-α and its cognate receptors TNF-R1 and 2. We used Ramos Burkitt's lymphoma cell line as a model system to study the direct effects of these cytokines on B cells. Treatment of Ramos cells with either TNF-α or CD40L, but not with interleukin (IL)- 4, interferon (IFN)-γ and transforming growth factor (TGF)-β, resulted in enhanced cell aggregation and enhancement of adherence to glass cover-slips. Scanning electron microscopy showed that Ramos cells have a polarized cell surface morphology and exhibit at least 3 cell surface morphological domains: microvilli, filopodia and ruffled membranes. The cells adhered to the glass matrix through multiple filopodia/podopodia-like cell processes and demonstrated distinct ruffled-like membrane projections on their opposite pole. Induction by TNF-α or CD40L, but not with IL-4, IFN-γ and TGF-β, resulted in increased number and complexity of both types of membrane projections. TNF-α and CD40L upregulated the expression of the adhesion molecule intercellular adhesion molecule-1 and the Fas receptor on Ramos cells, without affecting the expression levels of membrane immunoglobulin M or its secretion rate. Reverse transcriptase-polymerase chain reaction, and flow cytometry demonstrated that Ramos cells expressed TNF-R1 but very little if any TNF-R2, indicating that TNF-α exerted its effects on Ramos cells through the former receptor.

Original languageEnglish (US)
Pages (from-to)507-519
Number of pages13
JournalLeukemia and Lymphoma
Volume47
Issue number3
DOIs
StatePublished - Mar 1 2006

Keywords

  • B-lymphoma
  • Filopodia
  • ICAM-1
  • Ruffled membrane
  • Scanning electron microscopy
  • TNF receptors

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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