Inhibitory coreceptors activated by antigens but not by anti-Ig heavy chain antibodies install requirement of costimulation through CD40 for survival and proliferation of B cells

J Immunol. 2003 Aug 15;171(4):1835-43. doi: 10.4049/jimmunol.171.4.1835.

Abstract

Ag-induced B cell proliferation in vivo requires a costimulatory signal through CD40, whereas B cell Ag receptor (BCR) ligation by anti-Ig H chain Abs, such as anti-Ig micro H chain Ab and anti-Ig delta H chain Ab, alone induces proliferation of B cells in vitro, even in the absence of CD40 ligation. In this study, we demonstrate that CD40 signaling is required for survival and proliferation of B cells stimulated by protein Ags in vitro as well as in vivo. This indicates that the in vitro system represents B cell activation in vivo, and that protein Ags generate BCR signaling distinct from that by anti-Ig H chain Abs. Indeed, BCR ligation by Ags, but not by anti-Ig H chain Abs, efficiently phosphorylates the inhibitory coreceptors CD22 and CD72. When these coreceptors are activated, anti-Ig H chain Ab-stimulated B cells can survive and proliferate only in the presence of CD40 signaling. Conversely, treatment of Ag-stimulated B cells with anti-CD72 mAb blocks CD72 phosphorylation and induces proliferation, even in the absence of CD40 signaling. These results strongly suggest that activation of B cells by anti-Ig H chain Abs involves their ability to silence the inhibitory coreceptors, and that the inhibitory coreceptors install requirement of CD40 signaling for survival and proliferation of Ag-stimulated B cells.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibodies, Anti-Idiotypic* / pharmacology
  • Antigens / pharmacology*
  • Antigens, CD / metabolism
  • Antigens, CD / physiology*
  • Antigens, Differentiation, B-Lymphocyte / metabolism
  • Antigens, Differentiation, B-Lymphocyte / physiology*
  • B-Lymphocytes / cytology*
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • CD40 Antigens / physiology*
  • Cell Adhesion Molecules*
  • Cell Cycle / immunology
  • Cell Division / genetics
  • Cell Division / immunology
  • Cell Survival / genetics
  • Cell Survival / immunology
  • Cells, Cultured
  • Immunoglobulin Heavy Chains* / genetics
  • Immunoglobulin Heavy Chains* / immunology
  • Immunoglobulin lambda-Chains / genetics
  • Immunoglobulin lambda-Chains / immunology
  • Lectins / metabolism
  • Lectins / physiology*
  • Lymphocyte Activation / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nitrophenols / pharmacology
  • Phenylacetates
  • Phosphorylation
  • Receptors, Antigen, B-Cell / immunology
  • Receptors, Antigen, B-Cell / metabolism
  • Sialic Acid Binding Ig-like Lectin 2
  • Signal Transduction / genetics
  • Signal Transduction / immunology
  • Spleen / cytology
  • Spleen / immunology
  • Spleen / metabolism

Substances

  • Antibodies, Anti-Idiotypic
  • Antigens
  • Antigens, CD
  • Antigens, Differentiation, B-Lymphocyte
  • CD40 Antigens
  • CD72 protein, human
  • Cd22 protein, mouse
  • Cell Adhesion Molecules
  • Immunoglobulin Heavy Chains
  • Immunoglobulin lambda-Chains
  • Lectins
  • Nitrophenols
  • Phenylacetates
  • Receptors, Antigen, B-Cell
  • Sialic Acid Binding Ig-like Lectin 2
  • 4-hydroxy-5-nitrophenyl acetic acid