Clonal replacement sustains long-lived germinal centers primed by respiratory viruses.

TitleClonal replacement sustains long-lived germinal centers primed by respiratory viruses.
Publication TypeJournal Article
Year of Publication2023
Authorsde Carvalho RVH, Ersching J, Barbulescu A, Hobbs A, Castro TBR, Mesin L, Jacobsen JT, Phillips BK, Hoffmann H-H, Parsa R, Canesso MCecilia C, Nowosad CR, Feng A, Leist SR, Baric RS, Yang E, Utz PJ, Victora GD
Date Published2023 Jan 05
KeywordsAnimals, B-Lymphocytes, Clone Cells, COVID-19, Germinal Center, Influenza, Human, Mice, RNA Virus Infections, SARS-CoV-2

Germinal centers (GCs) form in secondary lymphoid organs in response to infection and immunization and are the source of affinity-matured B cells. The duration of GC reactions spans a wide range, and long-lasting GCs (LLGCs) are potentially a source of highly mutated B cells. We show that rather than consisting of continuously evolving B cell clones, LLGCs elicited by influenza virus or SARS-CoV-2 infection in mice are sustained by progressive replacement of founder clones by naive-derived invader B cells that do not detectably bind viral antigens. Rare founder clones that resist replacement for long periods are enriched in clones with heavily mutated immunoglobulins, including some with very high affinity for antigen, that can be recalled by boosting. Our findings reveal underappreciated aspects of the biology of LLGCs generated by respiratory virus infection and identify clonal replacement as a potential constraint on the development of highly mutated antibodies within these structures.

Alternate JournalCell
PubMed ID36565697

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