Significance The germinal center (GC) reaction generates high-affinity antibody–producing plasma cells and memory B cells that are pivotal for immune responses against pathogens and effective vaccination. However, it remains a challenging task to enhance GC reactions because increased antigen doses or repeated immunization, which should activate more B and T cells for GC formation, do not significantly augment antibody affinity. Here, we show that predetermined GC niches set the ceiling of GC numbers and thus limit GC responses. Clearance of the GC niche occupied by preexisting GC B cells may be a strategy to improve vaccine effectiveness or restore repressed antibody responses in autoimmune patients.