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International Immunology, Vol. 12, No. 6, 915-926, June 2000
© 2000 Japanese Society for Immunology

Alterations in splenic architecture and the localization of anti-double-stranded DNA B cells in aged mice

Ashlyn S. Eaton-Bassiri, Laura Mandik-Nayak, Su-jean Seo, Michael P. Madaio1, Michael P. Cancro2 and Jan Erikson

The Wistar Institute, Philadelphia, PA 19104, USA
1 Departments of 1Medicine, and
2 Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA

Correspondence to: J. Erikson

Aging is characterized by a decline in humoral immunity and a concommitant increased incidence of anti-DNA and other autoantibodies. To define how the regulation of autoreactive B cells is altered with age, we have used BALB/c mice with an Ig heavy H chain transgene to track the fate of anti-double-stranded (ds) DNA B cells in vivo. In young adult mice, anti-dsDNA B cells are developmentally arrested and excluded from the splenic B cell follicle, whereas in most aged mice they are mature and localize within the B cell follicle. Furthermore, we have detailed global changes in lymphoid architecture that accompany aging: CD4+ T cells are found not only in the periarteriolar lymphoid sheath, but also in the B cell follicles. Strikingly, these disruptions are similar to those that precede serum anti-dsDNA antibody expression in autoimmune MRL-lpr/lpr mice.

Keywords: anti-nuclear antibodies, autoimmunity, nephritis, tolerance

Transmitting editor: C. Paige


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