Kinetics of the tingible body macrophage response in mouse germinal center development and its depression with age

Although tingible body macrophages (TBM) have been recognized in germinal centers for over 100 years, their role in the germinal center response is not clear. In this study, the kinetics of the TBM response was quantitatively assessed and correlated with the kinetics of germinal center development in young mice. The TBM response in old mice (which have an age-related depression of germinal center development; Szakal et al., 1990) was analyzed for comparison. Young and old immune mice were challenged with human serum albumin and 0, 1, 3, 5, 7, 10, and 14 days later the popliteal and axillary lymph nodes were evaluated. Germinal centers were localized histochemically in alternate serial sections using horseradish peroxidase conjugated peanut agglutinin. TBM numbers were determined per germinal center on adjacent sections by the presence of tingible bodies or histochemically by using the monoclonal antibody Mac-2. Analysis of lymph nodes from young mice showed that TBM numbers decreased with the dissociation of preexisting germinal centers. TBM reappeared 5 days after challenge and the TBM kinetics paralleled the increase in size of de novo germinal centers. In fact, a constant ratio of one TBM to every 350-450 B cells was maintained from day 5 to day 10. In old lymph nodes, TBM were generally absent throughout germinal center development. The lack of TBM prior to germinal center development and their absence in aged mice are inconsistent with the concept that TBM are required for the induction of the germinal center reaction. However, the data are consistent with a role for TBM in regulating the magnitude of the germinal center reaction.