Two complementary features of humoral immune memory confer protection against the same or variant antigens
Name
van-beek-et-al-2022-two-complementary-features-of-humoral-immune-memory-confer-protection-against-the-same-or-variant.pdf
Description
Published version
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1 MB
Format
Adobe PDF
Checksum (MD5)
84bd469f333879d3e4c6136aab5af2de
Author(s)
Van Beek, Matthew
Nussenzweig, Michel C
Chakraborty, Arup K
Date Issued
September 13, 2022
Journal
Proceedings of the National Academy of Sciences
Publisher
Proceedings of the National Academy of Sciences
Citation
M. Van Beek, M.C. Nussenzweig, A.K. Chakraborty, Two complementary features of humoral immune memory confer protection against the same or variant antigens, Proc. Natl. Acad. Sci. U.S.A.119 (37) e2205598119.
Version
Final published version
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.
MIT Department
Massachusetts Institute of Technology. Department of Physics
Massachusetts Institute of Technology. Department of Chemistry
Massachusetts Institute of Technology. Institute for Medical Engineering & Science
Ragon Institute of MGH, MIT and Harvard
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Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1073/pnas.2205598119
