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Autoimmune alterations induced by the New Zealand Black Lbw2 locus in BWF1 mice

Academic Article
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Overview

authors

  • Haraldsson, M. K.
  • dela Paz, N. G.
  • Kuan, J. G.
  • Gilkeson, G. S.
  • Theofilopoulos, Argyrios
  • Kono, Dwight

publication date

  • April 2005

journal

  • Journal of Immunology  Journal

abstract

  • The New Zealand Black (NZB) Lbw2 locus (lupus NZB x New Zealand White (NZW) 2 locus) was previously linked to mortality and glomerulonephritis, but not to IgG autoantibodies, suggesting that it played a role in a later disease stage. To define its contribution, (NZB x NZW)F1 hybrids (BWF1) containing two, one, or no copies of this locus were generated. Lack of the NZB Lbw2 indeed reduced mortality and glomerulonephritis, but not serum levels of total and anti-DNA IgG Abs. There were, however, significant reductions in the B cell response to LPS, total and anti-DNA IgM and IgG Ab-forming cells, IgM Ab levels, and glomerular Ig deposits. Furthermore, although serum IgG autoantibody levels correlated poorly with kidney IgG deposits, the number of spontaneous IgG Ab-forming cells had a significant correlation. Genome-wide mapping of IgM anti-chromatin levels identified only Lbw2, and analysis of subinterval congenics tentatively reduced Lbw2 to approximately 5 Mb. Because no known genes associated with B cell activation and lupus are in this interval, Lbw2 probably represents a novel B cell activation gene. These findings establish the importance of Lbw2 in the BWF1 hybrid and indicate that Lbw2, by enhancing B cell hyperactivity, promotes the early polyclonal activation of B cells and subsequent production of autoantibodies.

subject areas

  • Animals
  • Autoantibodies
  • Autoimmunity
  • B-Lymphocytes
  • Base Sequence
  • Chromosome Mapping
  • Female
  • Gene Dosage
  • Genetic Linkage
  • Hybridization, Genetic
  • Immunoglobulin G
  • Immunoglobulin M
  • Kidney Glomerulus
  • Lipopolysaccharides
  • Lupus Erythematosus, Systemic
  • Lupus Nephritis
  • Lymphocyte Activation
  • Male
  • Mice
  • Mice, Congenic
  • Mice, Inbred NZB
  • Microsatellite Repeats
  • Phenotype
  • Spleen
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Identity

International Standard Serial Number (ISSN)

  • 0022-1767

PubMed ID

  • 15814738
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Additional Document Info

start page

  • 5065

end page

  • 5073

volume

  • 174

issue

  • 8

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