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

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 to limit autoimmune pathologies, 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 by wild-type B cells required TLR7, B cell receptor specificity, antigen presentation, and type I interferon signaling. The adoptive transfer model provides a tool for identifying early events in the breaking of B cell tolerance in autoimmunity. Editor's summary: Autoimmune diseases like systemic lupus erythematosus (SLE) initiate through a breakdown of self-tolerance resulting in germinal centers (GCs) that enable the emergence of new autoreactive B cell clones. Van den Broek et al. examined the early dynamics of this in murine SLE using parabiosis and adoptive transfer models to synchronize the entry of wild-type (WT) B cells into autoreactive GCs. WT B cells enter rapidly, clonally expand, and persist in autoreactive GCs and subsequently differentiate into autoantibody-producing B cells. Entry into autoreactive GCs by WT B cells was dependent on Toll-like receptor 7 and B cell receptor specificity as well as antigen presentation and type I IFN. —Christiana Fogg [ABSTRACT FROM AUTHOR]