Invasion of spontaneous germinal centers by naive B cells is rapid and persistent.

Autor:	van den Broek T; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Harvard Medical School, Boston; MA 02115, USA., Oleinika K; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Harvard Medical School, Boston; MA 02115, USA., Rahmayanti S; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Harvard Medical School, Boston; MA 02115, USA., Castrillon C; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Harvard Medical School, Boston; MA 02115, USA., van der Poel CE; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Harvard Medical School, Boston; MA 02115, USA., Carroll MC; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Harvard Medical School, Boston; MA 02115, USA.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2023 Jun 01. Date of Electronic Publication: 2023 Jun 01.
DOI:	10.1101/2023.05.30.542805
Abstrakt:	In autoreactive germinal centers (GC) initiated by a single rogue B cell clone, wild-type B cells expand and give rise to clones that target other autoantigens, known as epitope spreading. The chronic, progressive nature of epitope spreading calls for early interventions, but the kinetics and molecular requirements for wild-type B cell invasion and participation in GC remain largely unknown. With parabiosis and adoptive transfer approaches in a murine model of systemic lupus erythematosus, we demonstrate that wild-type B cells join existing GCs rapidly, clonally expand, persist, and contribute to autoantibody production and diversification. The invasion of autoreactive GCs required TLR7, B cell receptor specificity, antigen presentation, and type I interferon signaling. The adoptive transfer model provides a novel tool for identifying early events in the breaking of B cell tolerance in autoimmunity. Competing Interests: Competing interests: The authors declare that they have no competing interests.
Databáze:	MEDLINE
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