Distinctive Medullary and Germinal Center Proliferative Patterns in Mouse Lymph Nodes after Regional Primary and Secondary Stimulation with Tetanus Toxoid

In an attempt to gain more insight into antigen-induced generation of plasma cells and memory B cells, respectively, we compared medullary proliferative responses and germinal center development in popliteal lymph nodes of young adult mice with antibody production as a function of time after primary and secondary stimulation with fluid tetanus toxoid (FTT) via the hind leg footpads. Differences in the time course of primary and secondary antibody responses correlated with the time sequence and magnitude of medullary proliferative activity rather than with germinal center formation and growth. Initial labeling indices of lymphoid and plasmocytoid cells were determined after injection of 3H-thymidine. After primary antigenic stimulation, medullary-labeling indices showed moderate oscillations with a maximum (8%) on day 6 and subsequent variations above control levels to day 32. In contrast to this limited but sustained primary proliferative response, medullary-labeling indices after booster injection of the antigen rose to a sharp, high peak (30%) on day 3 and then fell abruptly to almost control values between days 5 and 6. Germinal center activity, as expressed in both numerical increase and expansion of individual centers, was at least as important after primary stimulation as after the booster injection, although the latter evoked formation of these structures 2 to 3 days earlier than the primary stimulus. Variations in numbers and total mass of germinal centers during the anamnestic response were characterized by a maximum on day 5, followed by a rapid decline to day 6, i.e., when serum antibody titers attained a high plateau, and a second rise to day 12. This pattern differed significantly from that after primary injection of FTT showing a more sustained germinal center deployment between days 6 and 14. These observations support the view suggested previously by other authors that germinal centers are predominantly involved in the generation of memory B cells, and do not contribute markedly to antibody production elicited by the same antigen which evoked their de novo formation and expansion.