title: Kinetics of germinal center development in lymph nodes of young and aging immune mice.
abstract: Recent findings imply that germinal center paucity in old mice, at least in part, results from a defect in the mechanisms responsible for the transport of antigens to lymphoid nodules (follicles) and the consequent impairment of the antigen retaining reticulum (ARR) of follicular dendritic cells (FDCs). The present objective was to observe the kinetics of lymph node germinal center development in old mice having antigen transport and ARR deficits. Germinal center development was monitored in popliteal (PLN) and axillary (AXLN) lymph nodes of 6-8 wk and 23-mo-old horseradish peroxidase (HRP) immune C57BL/6 mice. Using the selective binding of germinal center B cells for peanut agglutinin (PNA), germinal centers were identified in serial vibratome sections following histochemical labeling with PNA-peroxidase conjugates at times 0, 15 min, 1, 3, 5, and 10 days after footpad challenge with 8 micrograms HRP. To follow the fate of preexisting (environmental antigen-induced) germinal centers and the development of de novo (HRP-induced) germinal centers, it was essential to distinguish between these germinal centers. Accordingly, PNA positive germinal centers associated with HRP-retaining (peroxidase positive) ARR were identified as de novo germinal centers and germinal centers not associated with a peroxidase positive ARR were classified as preexisting germinal centers. Kinetic analysis of PNA positive germinal centers showed the following: 1) Preexisting, environmentally-induced germinal centers dissociated and disappeared by day 3 as indicated by a decline in their numbers after antigen injection: the process of germinal center dissociation remained unaffected by aging. 2) The latency of de novo germinal center appearance was approximately equal in duration (approximately 3 days) to the disappearance of pre-existing germinal centers. 3) The number and size of de novo HRP-induced germinal centers increased through the experimental period in young lymph nodes, but in old mice these parameters were depressed, resulting in a significant germinal center deficit. 4) The ratio of HRP-retaining ARR to de novo induced germinal centers was 1:1 in young and responder old mice. This ratio was not affected by aging. This finding favored the concept that antigen retention in ARR is a requirement of germinal center development. The observations supported our hypothesis that germinal center development, at least in part, depends on a normal antigen transport by showing that in aged mice with defective antigen transport-related ARR and iccosome deficits there is an impaired development of germinal centers.
authors.affiliation: Department of Anatomy, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298.
authors.forename: A K
authors.initials: AK
authors.lastname: Szakal
authors.forename: J K
authors.initials: JK
authors.lastname: Taylor
authors.forename: J P
authors.initials: JP
authors.lastname: Smith
authors.forename: M H
authors.initials: MH
authors.lastname: Kosco
authors.forename: G F
authors.initials: GF
authors.lastname: Burton
authors.forename: J J
authors.initials: JJ
authors.lastname: Tew
mesh_terms: D000375:Aging / Q000473:pathology*; D000818:Animals; D002452:Cell Count; D005260:Female; D007700:Kinetics; D008198:Lymph Nodes / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL