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Germinal Center and Extrafollicular B Cell Responses in Vaccination, Immunity, and Autoimmunity
Open accessAbstract
Activated B cells participate in either extrafollicular (EF) or germinal center (GC) responses. Canonical responses are composed of a short wave of plasmablasts (PBs) arising from EF sites, followed by GC producing somatically mutated memory B cells (MBC) and long-lived plasma cells. However, somatic hypermutation (SHM) and affinity maturation can take place at both sites, and a substantial fraction of MBC are produced prior to GC formation. Infection responses range from GC responses that persist for months to persistent EF responses with dominant suppression of GCs. Here, we review the current understanding of the functional output of EF and GC responses and the molecular switches promoting them. We discuss the signals that regulate the magnitude and duration of these responses, and outline gaps in knowledge and important areas of inquiry. Understanding such molecular switches will be critical for vaccine development, interpretation of vaccine efficacy and the treatment for autoimmune diseases.
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“The persistent clones expand without accumulating large numbers of additional mutations, indicating that clonal expansion of human memory B cells does not require re-entry into germinal centres and occurs in the activated B cell compartment17,27–31.”
From Naturally enhanced neutralizing breadth against SARS-CoV-2 one year after infection (2021) · cites this paper as [27]
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Metadata
- Authors
- Elsner, R. A., & Shlomchik, M. J.
- Affiliations
- University of Pittsburgh (US)
- Corresponding author
- Shlomchik, Mark J.
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2020-12
- Volume
- 53
- Issue
- 6
- Pages
- 1136-1150
- ISSN
- 1074-7613 (ISSN-L)
- PMC
- PMC7748291
- OpenAlex
- W3111108024
- Cited by
- 526
- References
- 207
- Citations by year
- 2026: 84 · 2025: 116 · 2024: 124 · 2023: 73 · 2022: 94 · 2021: 33
- FWCI
- 4.89
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases
- 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 reaction, somatic hypermutation, affinity maturation, memory B cells, plasmablasts, long-lived plasma cells, B cell activation, vaccine development, vaccine efficacy, autoimmunity, infection immunity
- MeSH terms
- Animals, Autoimmune Diseases, B-Lymphocytes, Humans, Immunity, Infections, Lymphocyte Activation, Plasma Cells, Vaccines, B-Lymphocyte Subsets, Immunoglobulin Class Switching, Germinal Center
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