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Identification of a b-cell differentiation factor(s) spontaneously produced by proliferating t-cells in murine lupus strains of the lpr-lpr genotype

Academic Article
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Overview

authors

  • Prudhomme, G. J.
  • Park, C. L.
  • Fieser, T. M.
  • Kofler, R.
  • Dixon, F. J.
  • Theofilopoulos, Argyrios

publication date

  • 1983

journal

  • Journal of Experimental Medicine  Journal

abstract

  • Lymph node and spleen cells of the autoimmune MRL/Mp-lpr/lpr mouse strain spontaneously produce (in the absence of mitogenic stimulation) a factor(s) that induces B cell differentiation. This factor is not produced by the congenic MRL/n mouse strain that lacks the lpr gene or by normal mouse strains. However, lymphoid cells of the B6-lpr/lpr (B6/1) strain also produce a B cell differentiation factor. Although the factor acts on resting B cells, its effect is greatly magnified by activating the B cells with anti-mu or lipopolysaccharide. MRL/l mice begin producing the factor as early as 1 mo of age but levels increase with age and appearance of lymphoproliferation. Cell depletion studies reveal that this factor is produced by T cells of the Lyt-1+2-phenotype. Because of its association with the lpr/lpr genotype, we term this B cell differentiation factor L-BCDF. Functional analysis of L-BCDF reveals that it acts regardless of cell density in culture and in the absence of interleukin 2 (IL-2). In fact, the increase in the production of L-BCDF by MRL/1 T cells with aging occurs concomitantly with a marked decrease in their ability to produce IL-2. No T cell replacing factor activity or B cell growth factor-like activity can be detected in MRL/l-derived supernatants. L-BCDF induces both IgM and IgG synthesis in lipopolysaccharide-activated B cells; however, it has a greater effect on IgG secretion. In particular, the production of IgG1, IgG2a, and IgG2b are markedly enhanced in the presence of L-BCDF. The spontaneous production of L-BCDF by T cells of SLE mice of lpr/lpr genotype suggests an association of this factor with autoimmunity.

subject areas

  • Aging
  • Animals
  • Autoimmune Diseases
  • B-Lymphocytes
  • Concanavalin A
  • Female
  • Genotype
  • Growth Substances
  • Immunoglobulin G
  • Immunoglobulin M
  • Interleukin-2
  • Interleukin-4
  • Lupus Erythematosus, Systemic
  • Lymphocyte Activation
  • Lymphokines
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • T-Lymphocytes
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Identity

International Standard Serial Number (ISSN)

  • 0022-1007

Digital Object Identifier (DOI)

  • 10.1084/jem.157.2.730

PubMed ID

  • 6600490
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Additional Document Info

start page

  • 730

end page

  • 742

volume

  • 157

issue

  • 2

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