ArticleProceedings of the National Academy of Sciences of the United States of America2022
Two complementary features of humoral immune memory confer protection against the same or variant antigens.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 24 citations in OpenAlex.
- Phased fragility and stability of non-genetic B cell states in the germinal center accelerate the genetic evolution of antibodies.Cell systems · 2026Article
- Integrated analysis of humoral and memory B-cell responses reveals distinct immune landscapes shaped by influenza vaccine platforms.NPJ vaccines · 2025Article
- Mastering Immunity: Antibody Feedback as a Driver of Germinal Center Fate and Vaccine Responses.European journal of immunology · 2025Review
- Mechanism for evolution of diverse autologous antibodies upon broadly neutralizing antibody therapy of people with HIV.Cell reports · 2025Article
- Article
- Enhanced and Prolonged Immunogenicity in Mice of Thermally Stabilized Fatty Acid-Conjugated Vaccine Antigen.Vaccines · 2025Article
- Factors determining the outcomes of immune imprinting after repeated orthoflavivirus infections.Frontiers in immunology · 2025Review
- Exponential decline, ceiling effect, downregulation, and T-cell response in immunoglobulin G antibody levels after messenger RNA vaccine boosters: a case report.Journal of medical case reports · 2024Article
- Ongoing evolution of SARS-CoV-2 drives escape from mRNA vaccine-induced humoral immunity.Cell reports. Medicine · 2024Article
- Minimal framework for optimizing vaccination protocols targeting highly mutable pathogens.Physical review. E · 2024Article
- Two-dose priming immunization amplifies humoral immunity by synchronizing vaccine delivery with the germinal center response.Science immunology · 2024Article
- Two-dose "extended priming" immunization amplifies humoral immune responses by synchronizing vaccine delivery with the germinal center response.bioRxiv : the preprint server for biology · 2023Article
- Functions of double-negative B cells in autoimmune diseases, infections, and cancers.EMBO molecular medicine · 2023Review
- Two complementary features of humoral immune memory confer protection against the same or variant antigens.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Antigen presentation dynamics shape the response to emergent variants like SARS-CoV-2 Omicron strain after multiple vaccinations with wild type strain.bioRxiv : the preprint server for biology · 2022Article
Corrections and comments
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Authors and funding
3 authors at 3 institutions in 1 country.
Funding
Abstract
The humoral immune response, a key arm of adaptive immunity, consists of B cells and their products. Upon infection or vaccination, B cells undergo a Darwinian evolutionary process in germinal centers (GCs), resulting in the production of antibodies and memory B cells. We developed a computational model to study how humoral memory is recalled upon reinfection or booster vaccination. We find that upon reexposure to the same antigen, affinity-dependent selective expansion of available memory B cells outside GCs (extragerminal center compartments [EGCs]) results in a rapid response made up of the best available antibodies. Memory B cells that enter secondary GCs can undergo mutation and selection to generate even more potent responses over time, enabling greater protection upon subsequent exposure to the same antigen. GCs also generate a diverse pool of B cells, some with low antigen affinity. These results are consistent with our analyses of data from humans vaccinated with two doses of a COVID-19 vaccine. Our results further show that the diversity of memory B cells generated in GCs is critically important upon exposure to a variant antigen. Clones drawn from this diverse pool that cross-react with the variant are rapidly expanded in EGCs to provide the best protection possible while new secondary GCs generate a tailored response for the new variant. Based on a simple evolutionary model, we suggest that the complementary roles of EGC and GC processes we describe may have evolved in response to complex organisms being exposed to evolving pathogen families for millennia.
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