Alterations in splenic architecture and the localization of anti-double-stranded DNA B cells in aged mice.
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.
Eaton-Bassiri
A S
AS
The Wistar Institute, Philadelphia, PA 19104, USA.
Mandik-Nayak
L
L
Seo
S J
SJ
Madaio
M P
MP
Cancro
M P
MP
Erikson
J
J
D000375:Aging / Q000276:immunology* / Q000473:pathology; D000818:Animals; D000974:Antibodies, Antinuclear / Q000032:analysis*; D001402:B-Lymphocytes / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D004247:DNA / Q000276:immunology*; D016130:Immunophenotyping; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009393:Nephritis / Q000209:etiology; D013154:Spleen / Q000473:pathology*; D019014:fas Receptor / Q000032:analysis
D000974:Antibodies, Antinuclear; D019014:fas Receptor; D004247:DNA