%0 Journal Article
%T Opposing effects of pre-existing antibody and memory T cell help on the dynamics of recall germinal centers.
%A Schiepers A
%A Van't Wout MFL
%A Hobbs A
%A Mesin L
%A Victora GD
%J Immunity
%V 57
%N 7
%D 2024 Jul 9
%M 38838672
%F 43.474
%R 10.1016/j.immuni.2024.05.009
%X Re-exposure to an antigen generates abundant antibody responses and drives the formation of secondary germinal centers (GCs). Recall GCs in mice consist almost entirely of naïve B cells, whereas recall antibodies derive overwhelmingly from memory B cells. Here, we examine this division between cellular and serum compartments. After repeated immunization with the same antigen, tetramer analyses of recall GCs revealed a marked decrease in the ability of B cells in these structures to bind the antigen. Boosting with viral variant proteins restored antigen binding in recall GCs, as did genetic ablation of primary-derived antibody-secreting cells through conditional deletion of Prdm1, demonstrating suppression of GC recall responses by pre-existing antibodies. In hapten-carrier experiments in which B and T cell specificities were uncoupled, memory T cell help allowed B cells with undetectable antigen binding to access GCs. Thus, antibody-mediated feedback steers recall GC B cells away from previously targeted epitopes and enables specific targeting of variant epitopes, with implications for vaccination protocols.