Distinct role of CD80 and CD86 in the regulation of the activation of B cell and B cell lymphoma

J Biol Chem. 2002 Mar 8;277(10):7766-75. doi: 10.1074/jbc.M105902200. Epub 2001 Nov 28.

Abstract

To date, not much has been known regarding the role of CD80 and CD86 molecules in signaling of B cells. The CD28/CTLA4 ligands, CD80 (B7-1) and CD86 (B7-2), are expressed on the surface of freshly isolated splenic B cells, and their expression is up-regulated by lipopolysaccharides. In the present study, we have investigated whether signaling via CD80/CD86 could alter the proliferation and immunoglobulin synthesis of B cells. Splenic B cells were stimulated with lipopolysaccharides in the presence of anti-B7-1 (16-10A1) and anti-B7-2 (GL1) monoclonal antibodies (mAbs). Exciting features observed during the study were that cross-linking of CD86 with GL1 enhanced the proliferation and production of IgG1 and IgG2a isotypes. In contrast, anti-B7-1 (16-10A1) mAb could efficiently block the proliferation and production of IgG1 and IgG2a. Furthermore, GL1 mAb could also induce the secretion of IgG isotypes from B cell lymphomas. Importantly, 16-10A1 could retard the growth of lymphomas and favored the up-regulation of pro-apoptotic molecules caspase-3, caspase-8, Fas, FasL, Bak, and Bax and down-regulation of anti-apoptotic molecule Bcl-x(L). In contrast, GL1 augmented the level of anti-apoptotic molecules Bcl-w and Bcl-x(L) and decreased the levels of pro-apoptotic molecule caspase-8, thereby providing a novel insight into the mechanism whereby triggering through CD80 and CD86 could deliver regulatory signals. Thus, this study is the first demonstration of a distinct signaling event induced by CD80 and CD86 molecules in B cell lymphoma. Finally, the significance of the finding is that CD80 provided negative signal for the proliferation and IgG secretion of normal B cells and B cell lymphomas. In contrast, CD86 encouraged the activity of B cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / metabolism
  • Antigens, CD / physiology*
  • Apoptosis
  • B-Lymphocytes / metabolism*
  • B7-1 Antigen / physiology*
  • B7-2 Antigen
  • Caspase 3
  • Caspase 8
  • Caspase 9
  • Caspases / metabolism
  • Cell Division
  • Cell Line
  • Cell Separation
  • Cross-Linking Reagents / pharmacology
  • Dose-Response Relationship, Drug
  • Dose-Response Relationship, Immunologic
  • Down-Regulation
  • Fas Ligand Protein
  • Female
  • Flow Cytometry
  • Humans
  • Immunoglobulin G / metabolism
  • Ligands
  • Lipopolysaccharides / metabolism
  • Lymphoma / metabolism
  • Lymphoma, B-Cell / metabolism*
  • Membrane Glycoproteins / metabolism
  • Membrane Glycoproteins / physiology*
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Protein Binding
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Signal Transduction
  • Time Factors
  • Tumor Cells, Cultured
  • Up-Regulation
  • bcl-2 Homologous Antagonist-Killer Protein
  • bcl-2-Associated X Protein
  • bcl-X Protein
  • fas Receptor / metabolism

Substances

  • Antibodies, Monoclonal
  • Antigens, CD
  • B7-1 Antigen
  • B7-2 Antigen
  • BAK1 protein, human
  • BAX protein, human
  • BCL2L1 protein, human
  • Bak1 protein, mouse
  • Bax protein, mouse
  • Bcl2l1 protein, mouse
  • CD86 protein, human
  • Cd86 protein, mouse
  • Cross-Linking Reagents
  • FASLG protein, human
  • Fas Ligand Protein
  • Fasl protein, mouse
  • Immunoglobulin G
  • Ligands
  • Lipopolysaccharides
  • Membrane Glycoproteins
  • Membrane Proteins
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2 Homologous Antagonist-Killer Protein
  • bcl-2-Associated X Protein
  • bcl-X Protein
  • fas Receptor
  • CASP3 protein, human
  • CASP8 protein, human
  • CASP9 protein, human
  • Casp3 protein, mouse
  • Casp8 protein, mouse
  • Casp9 protein, mouse
  • Caspase 3
  • Caspase 8
  • Caspase 9
  • Caspases