A Temporal Switch in the Germinal Center Determines Differential Output of Memory B and Plasma Cells
Open accessAbstract
There is little insight into or agreement about the signals that control differentiation of memory B cells (MBCs) and long-lived plasma cells (LLPCs). By performing BrdU pulse-labeling studies, we found that MBC formation preceded the formation of LLPCs in an adoptive transfer immunization system, which allowed for a synchronized Ag-specific response with homogeneous Ag-receptor, yet at natural precursor frequencies. We confirmed these observations in wild-type (WT) mice and extended them with germinal center (GC) disruption experiments and variable region gene sequencing. We thus show that the GC response undergoes a temporal switch in its output as it matures, revealing that the reaction engenders both MBC subsets with different immune effector function and, ultimately, LLPCs at largely separate points in time. These data demonstrate the kinetics of the formation of the cells that provide stable humoral immunity and therefore have implications for autoimmunity, for vaccine development, and for understanding long-term pathogen resistance.
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Primary alum-adjuvanted protein immunization of mice typically leads to germinal centre responses that peak 1-2 weeks after immunization and contract at least 10-fold within 5-7 weeks.
“Primary alum-adjuvanted protein immunization of mice typically leads to germinal centre responses that peak 1–2 weeks after immunization and contract at least 10-fold within 5–7 weeks24–26.”
From SARS-CoV-2 mRNA vaccines induce persistent human germinal centre responses (2021) · cites this paper as [25]
Persistence of S-binding germinal centre B cells and plasmablasts in draining lymph nodes is a positive indicator for induction of long-lived plasma cell responses.
“The persistence of S-binding germinal centre B cells and plasmablasts in draining lymph nodes is a positive indicator for induction of long-lived plasma cell responses25.”
From SARS-CoV-2 mRNA vaccines induce persistent human germinal centre responses (2021) · cites this paper as [25]
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- Authors
- Weisel, F. J., Zuccarino-Catania, G. V., Chikina, M., & Shlomchik, M. J.
- Affiliations
- University of Pittsburgh (US)
- Yale University (US)
- Corresponding author
- Shlomchik, Mark J.
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2016-01
- Volume
- 44
- Issue
- 1
- Pages
- 116-130
- ISSN
- 1074-7613 (ISSN-L)
- PMC
- PMC4724390
- OpenAlex
- W2239291357
- Cited by
- 524
- References
- 61
- Citations by year
- 2026: 36 · 2025: 31 · 2024: 49 · 2023: 49 · 2022: 68 · 2021: 69 · 2020: 58 · 2019: 60 · 2018: 37 · 2017: 45 · 2016: 21
- FWCI
- 33.08
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (R01-Al46303)
- Deutsche Forschungsgemeinschaft (WE 4752/1-1)
- National Science Foundation
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- germinal center, memory B cells, long-lived plasma cells, B cell differentiation, humoral immunity, autoimmunity, vaccine development
- MeSH terms
- Animals, B-Lymphocytes, Cell Differentiation, Cell Separation, Flow Cytometry, Immunohistochemistry, Immunologic Memory, Mice, Inbred BALB C, Mice, Transgenic, Plasma Cells, Time Factors, B-Lymphocyte Subsets, Germinal Center, Adoptive Transfer, Mice, Immunity, Humoral, Enzyme-Linked Immunospot Assay
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