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Analysis of central b cell tolerance in autoimmune-prone mrl/lpr mice bearing autoantibody transgenes

Academic Article
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Overview

authors

  • Rubio, C. F.
  • Kench, J.
  • Russell, D. M.
  • Yawger, R.
  • Nemazee, David

publication date

  • July 1996

journal

  • Journal of Immunology  Journal

abstract

  • The effect of the autoimmune prone MRL/lpr (H-2k) genetic background on central B cell tolerance was studied in mice bearing 3-83 (anti-H-2Kk) Ig heavy and light chain transgenes. B cells bearing the dominant, transgene-encoded anti-H-2Kk specificity were tolerized appropriately on the MRL/lpr genetic background. Nevertheless, mice developed disease traits characteristic of the MRL/lpr strain, including lymphadenopathy and elevated levels of IgG dsDNA autoantibodies. Two transgenic lines were examined in this analysis: 3-83 mu delta, which expresses IgM and IgD forms of the 3-83 Ab, and Tol 1, which expresses only the IgM form of 3-83. The results obtained differed somewhat between the two transgenic lines. Crosses using 3-83 mu(delta) mice never demonstrated any defects in B cell self-tolerance to H-2Kk. Similarly, no Kk autoantibody production was seen in Tol 1 mice that were backcrossed onto the MRL/lpr genetic background and maintained in a specific pathogen-free facility. However, a subset of Tol 1/MRL/lpr mice that were housed in a conventional mouse facility demonstrated significant transgene-derived anti-Kk autoantibodies. Overall, these results suggest that there is no general defect in central B cell tolerance in MRL/lpr mice, despite their defect in the fas gene. These findings suggest similarities between the MRL/lpr T and B cell systems, because both fail to manifest clear central tolerance defects, but they nevertheless promote hyperplasia and autoimmunity in the peripheral immune system.

subject areas

  • Animals
  • Antibodies, Antinuclear
  • Autoantibodies
  • Autoimmune Diseases
  • B-Lymphocytes
  • Base Sequence
  • Crosses, Genetic
  • DNA
  • H-2 Antigens
  • Immune Tolerance
  • Immunoglobulins
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Mice, Transgenic
  • Molecular Sequence Data
  • Transgenes
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Identity

International Standard Serial Number (ISSN)

  • 0022-1767

PubMed ID

  • 8683157
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Additional Document Info

start page

  • 65

end page

  • 71

volume

  • 157

issue

  • 1

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