Preferential Presentation of High-Affinity Immune Complexes in Germinal Centers Can Explain How Passive Immunization...

Passive immunization (PI) with external antibodies has been used classically for rapid but temporary alleviation of disease. Transcending this role, recent studies have shown PI to induce lasting improvements in natural antibody production, suggesting that PI could become a powerful tool to engineer humoral responses. We propose a mechanism with which PI can alter the humoral response. Antigen-specific B cells evolve and get selected in germinal centers (GCs) on the basis of their ability to acquire antigen from antibody-antigen complexes presented in GCs. When external antibodies of high affinity for antigen are used, they form the majority of the complexes in GCs, letting only B cells with even higher affinities be selected. Using an in silico GC reaction model, we show that this mechanism explains the improved humoral responses following PI. The model also synthesizes several independent experimental observations, indicating the robustness of the mechanism, and proposes tunable handles to optimize PI.