Preferential Presentation of High-Affinity Immune Complexes in Germinal Centers Can Explain How Passive Immunization Improves the Humoral Response

oleh: Amar K. Garg, Rajat Desikan, Narendra M. Dixit

Format: Article
Diterbitkan: Elsevier 2019-12-01

Deskripsi

Summary: 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 forĀ 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. : Passive immunization can induce lasting improvements in endogenous antibody responses. Garg etĀ al. develop an in silico model of the germinal center (GC) reaction that explains this puzzling phenomenon. Further, the model unravels a quality-quantity trade-off constraining the GC reaction, synthesizes diverse experimental observations, and suggests strategies to optimize interventions. Keywords: affinity maturation, quality-quantity trade-off, B cell selection, antibody feedback, passive immunization, germinal center, mathematical modeling, stochastic simulations, vaccine design, humoral response