Scientific article

Lessons from BXSB and related mouse models

Published inInternational reviews of immunology, vol. 19, no. 4-5, p. 447-472
Publication date2000

The BXSB murine strain spontaneously develops an autoimmune syndrome with features of systemic lupus erythematosus (SLE) that affects males much earlier than females, due to the presence of an as yet unidentified mutant gene located on its Y chromosome, designated Yaa (Y-linked autoimmune acceleration). The Yaa gene by itself is unable to induce significant autoimmune responses in mice without an apparent SLE background, while it can induce and accelerate the development of an SLE in combination with autosomal susceptibility alleles present in lupus-prone mice. Although the genes encoded within or closely linked to the MHC locus play an important role in the development or protection of SLE, the MHC effect can be completely masked by the presence of the Yaa gene in mice highly predisposed to SLE. The role of the Yaa gene for the acceleration of SLE is apparently two-fold; it enhances overall autoimmune responses against autoantigens to which mice respond relatively weakly, and promotes Th 1 responses against autoantigens to which mice respond relatively well, leading to the production of more pathogenic autoantibodies, i.e., FcgammaR-fixing IgG2a and cryoglobulin IgG3 autoantibodies. Yaa+ - Yaa- double bone marrow chimera experiments revealed that the Yaa defect is expressed in B cells, but not in T cells, and that T cells from non-autoimmune mice are capable of providing help for autoimmune responses by collaborating Yaa+ B cells. We speculate that the Yaa defect may decrease the threshold for antigen receptor-dependent stimulation, leading to the triggering and excessive stimulation of autoreactive T and B cells.

  • Animals
  • Antiphospholipid Syndrome/etiology
  • Autoantibodies/biosynthesis
  • Autoimmunity
  • Disease Models, Animal
  • Genetic Predisposition to Disease
  • H-2 Antigens/genetics
  • Humans
  • Lupus Erythematosus, Systemic/ genetics
  • Mice
  • Y Chromosome
Affiliation Not a UNIGE publication
Citation (ISO format)
IZUI, Shozo et al. Lessons from BXSB and related mouse models. In: International reviews of immunology, 2000, vol. 19, n° 4-5, p. 447–472. doi: 10.3109/08830180009055507
Updates (1)
ISSN of the journal0883-0185

Technical informations

Creation08/27/2010 1:33:42 PM
First validation08/27/2010 1:33:42 PM
Update time03/14/2023 4:02:24 PM
Status update03/14/2023 4:02:24 PM
Last indexation10/18/2023 11:16:47 AM
All rights reserved by Archive ouverte UNIGE and the University of GenevaunigeBlack