Involvement of CD100, a lymphocyte semaphorin, in the activation of the human immune system via CD72: implications for the regulation of immune and inflammatory responses

Int Immunol. 2003 Aug;15(8):1027-34. doi: 10.1093/intimm/dxg098.

Abstract

CD100/Sema4D belongs to the semaphorin family, factors known to act as repulsive cues for axons during neuronal development. Mouse CD100 plays a crucial role in both humoral and cellular immunity through ligation of the lymphocyte receptor, CD72. It remains controversial, however, whether human CD100 can function through human CD72 in a manner similar to mouse CD100. To determine the function of human CD100, we generated a recombinant soluble human CD100 protein comprised of the extracellular region of human CD100 fused to the human IgG1 Fc region (hCD100-Fc). hCD100-Fc specifically binds to cells expressing human CD72. As observed previously in the mouse, hCD100-Fc induces the tyrosine dephosphorylation of human CD72, leading to the dissociation of SHP-1 from the CD72 cytoplasmic tail. Consistent with findings for mouse CD100, hCD100-Fc exerts a co-stimulatory effect on B cells and dendritic cells that are stimulated with anti-CD40 mAb. Furthermore, both hCD100-Fc and anti-human CD72 agonistic mAb induce the production of the pro-inflammatory cytokines tumor necrosis factor-alpha, IL-6 and IL-8, even in the absence of anti-CD40 mAb. Collectively, our findings not only demonstrate that human CD100, interacting with human CD72, can function as a ligand in a manner similar to mouse CD100, but also suggest the involvement of human CD100 in inflammatory responses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / genetics
  • Antigens, CD / immunology
  • Antigens, CD / physiology*
  • Antigens, Differentiation, B-Lymphocyte / genetics
  • Antigens, Differentiation, B-Lymphocyte / immunology
  • Antigens, Differentiation, B-Lymphocyte / physiology*
  • B-Lymphocytes / immunology
  • CD40 Antigens / immunology
  • CHO Cells
  • COS Cells
  • Cell Division / physiology
  • Chlorocebus aethiops
  • Cloning, Molecular
  • Cricetinae
  • Dendritic Cells / metabolism
  • Flow Cytometry
  • Gene Expression Regulation
  • Humans
  • Immune System / physiology*
  • Inflammation / physiopathology*
  • Interleukin-12 / analysis
  • Interleukin-12 / metabolism
  • Interleukin-6 / analysis
  • Interleukin-6 / metabolism
  • Interleukin-8 / analysis
  • Interleukin-8 / metabolism
  • Intracellular Signaling Peptides and Proteins
  • Lymphocyte Activation / immunology
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / immunology
  • Membrane Glycoproteins / physiology*
  • Monocytes / metabolism
  • Nerve Tissue Proteins*
  • Palatine Tonsil / cytology
  • Protein Binding
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6
  • Protein Tyrosine Phosphatases / metabolism
  • Receptors, Cell Surface*
  • Recombinant Fusion Proteins / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Semaphorins*
  • Transfection
  • Tumor Necrosis Factor-alpha / analysis
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Antigens, CD
  • Antigens, Differentiation, B-Lymphocyte
  • CD100 antigen
  • CD40 Antigens
  • CD72 protein, human
  • Interleukin-6
  • Interleukin-8
  • Intracellular Signaling Peptides and Proteins
  • Membrane Glycoproteins
  • Nerve Tissue Proteins
  • PLXNB1 protein, human
  • Plxnb1 protein, mouse
  • Receptors, Cell Surface
  • Recombinant Fusion Proteins
  • Semaphorins
  • Tumor Necrosis Factor-alpha
  • Interleukin-12
  • PTPN6 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6
  • Protein Tyrosine Phosphatases
  • Ptpn6 protein, mouse