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

ABSTRACT: 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.

SUBMITTER: van den Broek T

PROVIDER: S-EPMC10312503 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

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

van den Broek T T Oleinika K K Rahmayanti S S Castrillon C C van der Poel C E CE Carroll M C MC

bioRxiv : the preprint server for biology 20230601

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 de ...[more]

PMID: 37398148

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