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Liver-expressed Igκ superantigen induces tolerance of polyclonal B cells by clonal deletion not κ to λ receptor editing

Academic Article
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Overview

related to degree

  • Duong, Bao Hoa, Ph.D. in Macromolecular and Cellular Structure and Chemistry, Scripps Research 2003 - 2009

authors

  • Ota, Takayuki
  • Ota, M.
  • Duong, Bao Hoa
  • Gavin, Amanda
  • Nemazee, David

publication date

  • March 2011

journal

  • Journal of Experimental Medicine  Journal

abstract

  • Little is know about the nature of peripheral B cell tolerance or how it may vary in distinct lineages. Although autoantibody transgenic studies indicate that anergy and apoptosis are involved, some studies claim that receptor editing occurs. To model peripheral B cell tolerance in a normal, polyclonal immune system, we generated transgenic mice expressing an Igκ-light chain-reactive superantigen targeted to the plasma membrane of hepatocytes (pAlb mice). In contrast to mice expressing κ superantigen ubiquitously, in which κ cells edit efficiently to λ, in pAlb mice, κ B cells underwent clonal deletion. Their κ cells failed to populate lymph nodes, and the remaining splenic κ cells were anergic, arrested at a semi-mature stage without undergoing receptor editing. In the liver, κ cells recognized superantigen, down-regulated surface Ig, and expressed active caspase 3, suggesting ongoing apoptosis at the site of B cell receptor ligand expression. Some, apparently mature, κ B1 and follicular B cells persisted in the peritoneum. BAFF (B cell-activating factor belonging to the tumor necrosis factor family) overexpression rescued splenic κ B cell maturation and allowed κ cells to populate lymph nodes. Our model facilitates analysis of tissue-specific autoimmunity, tolerance, and apoptosis in a polyclonal B cell population. The results suggest that deletion, not editing, is the major irreversible pathway of tolerance induction among peripheral B cells.

subject areas

  • Animals
  • Apoptosis
  • Autoimmunity
  • B-Lymphocytes
  • Bacterial Outer Membrane Proteins
  • Clonal Deletion
  • Hepatocytes
  • Immunoglobulin kappa-Chains
  • Liver
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Porins
  • Receptors, Opioid, kappa
  • Receptors, Virus
  • Superantigens
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Identity

PubMed Central ID

  • PMC3058582

International Standard Serial Number (ISSN)

  • 0022-1007

Digital Object Identifier (DOI)

  • 10.1084/jem.20102265

PubMed ID

  • 21357741
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Additional Document Info

start page

  • 617

end page

  • 629

volume

  • 208

issue

  • 3

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