SARS Spike Protein Induces Phenotypic Conversion of Human B Cells to Macrophage-Like Cells

Mol Immunol. 2010 Oct;47(16):2575-86. doi: 10.1016/j.molimm.2010.06.014. Epub 2010 Jul 27.

Abstract

Massive aggregations of macrophages are frequently detected in afflicted lungs of patients with severe acute respiratory syndrome-associated coronavirus (SARS-CoV) infection. In vitro, ectopic expression of transcription factors, in particular CCAAT/enhancer-binding protein alpha (C/EBPα) and C/EBPβ, can convert B cells into functional macrophages. However, little is known about the specific ligands responsible for such phenotype conversion. Here, we investigated whether spike protein of SARS-CoV can act as a ligand to trigger the conversion of B cells to macrophages. We transduced SARS-CoV spike protein-displayed recombinant baculovirus (SSDRB), vAtEpGS688, into peripheral B cells and B lymphoma cells. Cell surface expression of CD19 or Mac-1 (CD11b) was determined by flow cytometry. SSDRB-mediated changes in gene expression profiles of B lymphoma cells were analyzed by microarray. In this report, we showed that spike protein of SARS virus could induce phenotypic conversion of human B cells, either from peripheral blood or B lymphoma cells, to macrophage-like cells that were steadily losing the B-cell marker CD19 and in turn expressing the macrophage-specific marker Mac-1. Furthermore, we found that SSDRB enhanced the expression of CD86, hypoxia-inducible factor-1α (HIF1α), suppressor of cytokine signaling (SOCS or STAT-induced STAT inhibitor)-3, C/EBPβ, insulin-like growth factor-binding protein 3 (IGFBP3), Krüpple-like factor (KLF)-5, and CD54, without marked influence on C/EBPα or PU.1 expression in transduced cells. Prolonged exposure to hypoxia could also induce macrophage-like conversion of B cells. These macrophage-like cells were defective in phagocytosis of red fluorescent beads. In conclusion, our results suggest that conversion of B cells to macrophage-like cells, similar to a pathophysiological response, could be mediated by a devastating viral ligand, in particular spike protein of SARS virus, or in combination with severe local hypoxia, which is a condition often observed in afflicted lungs of SARS patients.

MeSH terms

  • Animals
  • B-Lymphocytes / immunology*
  • Cell Line
  • Gene Expression Profiling
  • Humans
  • Lymphoma, B-Cell / immunology
  • Macrophages / immunology*
  • Male
  • Membrane Glycoproteins / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Phenotype
  • Recombinant Proteins / immunology
  • SARS Virus / immunology*
  • Spike Glycoprotein, Coronavirus
  • Viral Envelope Proteins / immunology*

Substances

  • Membrane Glycoproteins
  • Recombinant Proteins
  • Spike Glycoprotein, Coronavirus
  • Viral Envelope Proteins