Spatial confinement promotes germinal center diversity and tempers immunodominance

Germinal centers (GCs) form as confined clusters of motile cells within individual lymphoid follicles. The role of confinement in GC B cell evolutionary events is unknown. Here, using mice with reduced GC confinement because of deficiency in Gα13-dependent G-protein-coupled receptor signaling, we observed GC-GC trafficking in confinement-defective lymph nodes (LNs). In multicolor clonal lineage tracing mice, de-confined GCs minimally diversified their color palettes with respect to one another. Spatial B cell receptor sequencing revealed greater clonal crossover between neighboring GCs in the setting of dispersal. The total GC B cell repertoire of LNs with inter-GC exchange also decreased in overall diversity because of increased skewing toward top clones. As an outcome, LNs with de-confined GCs more strongly favored clones responding to accessible epitopes while losing clones binding to other portions of antigen. Together, our findings suggest that confinement supports antibody breadth by moderating the spread of dominant clones and preserving unique trajectories in individual GC responses.