What is it about?

In an era of predicted recurring pandemics the ability to produce highly effective vaccines that provide long-lived protection from pathogens and their mutant variants will be critical. We know that highly successful vaccines induce memory B cells (MBCs) that provide life-long protection from re-infection by the original pathogen as well as from variants of that pathogen. However, human MBCs are a heterogeneous cell population, and it is not yet known which MBC subsets function to control homologous versus variant pathogen infections. In our manuscript we provide evidence that two different MBC subsets play distinct yet complementary roles in response to pathogen re-challenge. One subpopulation, IgG+ MBCs, differentiate into plasma cells ensuring the immediate production of antibodies to the original pathogen and closely related pathogens and the second subpopulation, IgM+ MBCs, produce new variant-specific MBCs through mutation and selection. In addition we provide evidence that the MBC’s expression of B cell receptors of the IgG versus IgM type dictates their ability to respond to the original pathogen versus variants of that pathogen.

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Why is it important?

We believe our discovery of distinct MBC subsets that dictate pathogen-driven fates upon challenge will have an impact on the design of vaccines that ensure protection against homologous and variant pathogen challenge, the gold standard of vaccine development.


Our study adds to our understanding of the cellular basis of human immunological memory. This is critical as at present our knowledge of the composition of the human naïve B cell compartment is limited, in part because most of what we know about the mammalian immune system has come from studies in inbred mice. For decades, mice provided models in which the basic mechanisms underlying the complex workings of the immune system were deciphered. These were extraordinarily productive years in which the basic framework of the cellular and molecular mechanisms that underlie immune responses were established, providing critical insights necessary to translate this knowledge into therapies for human diseases including cancers and autoimmunity. However, we do not yet know how well the knowledge gained from the mouse immune system can be reliably translated into a comprehensive picture of the human immune system. Indeed, despite numerous important strides in human medicine based on insights gained in mouse models, predictions for human therapies and vaccines from mouse studies have more often than not been disappointing. Given the obvious, that humans are not mice and the large gaps in our knowledge of the human immune system, it is likely that direct investigations into human immunology will be critical to our ability to develop effective vaccines.


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This page is a summary of: Isotype switching in human memory B cells sets intrinsic antigen-affinity thresholds that dictate antigen-driven fates, Proceedings of the National Academy of Sciences, March 2024, Proceedings of the National Academy of Sciences,
DOI: 10.1073/pnas.2313672121.
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