Split tolerance in peripheral B cell subsets in mice expressing a low level of Igkappa-reactive ligand

J Immunol. 2006 Jan 15;176(2):939-48. doi: 10.4049/jimmunol.176.2.939.

Abstract

Peripheral B cell tolerance differs from central tolerance in anatomic location, in the stage of B cell development, and in the diversity of Ag-responsive cells. B cells in secondary lymphoid organs are heterogeneous, including numerous subtypes such as B-1, marginal zone, transitional, and follicular B cells, which likely respond differently from one another to ligand encounter. We showed recently that central B cell tolerance mediated by receptor editing was induced in mice carrying high levels of a ubiquitously expressed kappa-macroself Ag, a synthetic superantigen reactive to Igkappa. In this study, we characterize a new transgenic line that has a distinctly lower expression pattern from those described previously; the B cell tolerance phenotype of these mice is characterized by the presence of significant numbers of immature kappa+ B cells in the spleen, the loss of mature follicular and marginal zone B cells, the persistence of kappa+ B-1 cells in the peritoneal cavity, and significant levels of serum IgM,kappa. These findings suggest distinct signaling thresholds for tolerance among peripheral B cell subsets reactive with an identical ligand.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • B-Lymphocyte Subsets / cytology
  • B-Lymphocyte Subsets / immunology*
  • B-Lymphocyte Subsets / metabolism
  • Bromodeoxyuridine / metabolism
  • Cell Differentiation
  • Clonal Deletion
  • Genes, Immunoglobulin
  • Immune Tolerance*
  • Immunoglobulin kappa-Chains / metabolism*
  • Ligands
  • Lymphoid Tissue / cytology
  • Lymphoid Tissue / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Phenotype
  • Radiation Chimera / genetics
  • Radiation Chimera / immunology
  • Signal Transduction
  • Spleen / cytology
  • Spleen / immunology

Substances

  • Immunoglobulin kappa-Chains
  • Ligands
  • Bromodeoxyuridine