In vivo VL-targeted activation-induced apoptotic supraclonal deletion by a microbial B cell toxin.

  • Goodyear C
  • Narita M
  • Silverman G
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Abstract

To interfere with host immune responses, some microbial pathogens produce proteins with the properties of superantigens, which can interact via conserved V region framework subdomains of the Ag receptors of lymphocytes rather than the complementarity-determining region involved in the binding of conventional Ags. In recent studies, we have elucidated how a model B cell superantigen affects the host immune system by targeting a conserved V(H) site on the Ag receptors of B lymphocytes. To determine whether these findings represent a general paradigm, we investigated the in vivo immunobiologic properties of protein L of Peptostreptococcus magnus (PpL), a microbial Ig-binding protein specific for a V region site on Ig L chains. Our studies confirmed that PpL binding is restricted to a subset of murine Vkappa-expressing B cells, and found that B cells with stronger PpL-binding activity are associated with certain B cell subsets: splenic marginal zone (CD21(high) CD23(low)), splenic CD1(+), peritoneal B-1a (IgD(low) CD5(+)), and CD21(high) CD24(high) B cells in peripheral lymph nodes, mesenteric lymph nodes, and Peyer's patches. Infusion of PpL triggered a sequence of events in B cell receptor (BCR)-targeted B cells, with rapid down-regulation of BCR, the induction of an activation phenotype, and limited rounds of proliferation. Apoptosis followed through a process heralded by the dissipation of mitochondrial membrane potential, the induction of the caspase pathway, DNA fragmentation, and the deposition of B cell apoptotic bodies. These studies define a common pathway by which microbial toxins that target V region-associated BCR sites induce programmed cell death.

Author-supplied keywords

  • Adoptive Transfer
  • Animals
  • Antibody
  • Antigen
  • Apoptosis
  • Apoptosis: immunology
  • B-Cell
  • B-Cell: biosynthesis
  • B-Cell: metabolism
  • B-Lymphocyte Subsets
  • B-Lymphocyte Subsets: cytology
  • B-Lymphocyte Subsets: immunology
  • B-Lymphocyte Subsets: metabolism
  • B-Lymphocyte Subsets: transplantation
  • Bacterial Proteins
  • Bacterial Proteins: administration & dosage
  • Bacterial Proteins: metabolism
  • Bacterial Proteins: toxicity
  • Bacterial Toxins
  • Bacterial Toxins: administration & dosage
  • Bacterial Toxins: metabolism
  • Bacterial Toxins: toxicity
  • Binding Sites
  • Cell Separation
  • Clonal Deletion
  • Clonal Deletion: immunology
  • Immunoglobulin Light Chains
  • Immunoglobulin Light Chains: metabolism
  • Immunoglobulin Variable Region
  • Immunoglobulin Variable Region: metabolism
  • Immunoglobulin kappa-Chains
  • Immunoglobulin kappa-Chains: biosynthesis
  • Immunoglobulin kappa-Chains: metabolism
  • Inbred C57BL
  • Injections
  • Intraperitoneal
  • Lymphocyte Activation
  • Lymphocyte Activation: immunology
  • Mice
  • Mutant Strains
  • Peptostreptococcus
  • Peptostreptococcus: immunology
  • Protein Binding
  • Protein Binding: immunology
  • Receptors
  • Transgenic

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Authors

  • Carl S Goodyear

  • Masami Narita

  • Gregg J Silverman

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