Severe impairment of B cell function in lpr/lpr mice expressing transgenic Fas selectively on B cells

Int Immunol. 1999 Jul;11(7):1035-42. doi: 10.1093/intimm/11.7.1035.


Transgenic lpr/lpr mice expressing functional Fas selectively on B cells were produced in an attempt to elucidate the role of Fas on B cells in the regulation of autoantibody production. The homozygous lpr/lpr mice carrying the transgene did not produce anti-double-stranded DNA antibodies throughout their lives, whereas the development of abnormal lpr T cells (double negative, B220(+)) was not suppressed. Further analyses, however, revealed that the expression of the transgenic Fas on B cells of lpr/lpr homozygous mice resulted in severe impairment of the B cell function. The defect was characterized by a decrease in the number of mature peripheral B cells, a reduction in the serum Ig level and the total failure of B cells to mount antibody responses to stimulations of T-dependent as well as T-independent antigens. Such a defect was prominent only when the transgene was expressed on the lpr/lpr homozygous background. On the contrary, B cells of the transgenic lpr/lpr mice were shown to be capable of producing Ig when stimulated with anti-CD40 in the presence of IL-4 and IL-5. Furthermore, lpr/lpr T cells showed enhanced non-specific cytolytic activity. These observations suggested that the observed B cell defect was probably attributable to the destruction of activated B cells expressing transgenic Fas by aggressive lpr/lpr T cells.

MeSH terms

  • Animals
  • Autoantibodies / biosynthesis
  • Autoimmune Diseases / genetics*
  • Autoimmune Diseases / metabolism
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • B-Lymphocytes / pathology
  • DNA, Complementary / genetics
  • DNA, Complementary / immunology
  • DNA, Complementary / metabolism
  • Female
  • Gene Expression
  • Immunoglobulins / biosynthesis
  • Immunoglobulins / blood
  • Lymphocyte Count
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C3H
  • Mice, Inbred MRL lpr
  • Mice, Transgenic
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • Transgenes / immunology
  • fas Receptor / biosynthesis
  • fas Receptor / genetics
  • fas Receptor / immunology
  • fas Receptor / physiology*


  • Autoantibodies
  • DNA, Complementary
  • Immunoglobulins
  • fas Receptor