Tertiary Lymphoid Structures Sustain Cutaneous B cell Activity in Hidradenitis Suppurativa

Background Hidradenitis suppurativa (HS) skin lesions are highly inflammatory and characterized by a large immune infiltrate. While B cells and plasma cells comprise a major component of this immune milieu the biology and contribution of these cells in HS pathogenesis is unclear. Objective We aimed to investigate the dynamics and microenvironmental interactions of B cells within cutaneous HS lesions. Methods We combined histological analysis, single-cell RNA-sequencing (scRNAseq), and spatial transcriptomic profiling of HS lesions to define the tissue microenvironment relative to B cell activity within this disease. Results Our findings identify tertiary lymphoid structures (TLS) within HS lesions and describe organized interactions between T cells, B cells, antigen presenting cells and skin stroma. We find evidence that B cells within HS TLS actively undergo maturation, including participation in germinal center reactions and class switch recombination. Moreover, skin stroma and accumulating T cells are primed to support the formation of TLS and facilitate B cell recruitment during HS. Conclusion Our data definitively demonstrate the presence of TLS in lesional HS skin and point to ongoing cutaneous B cell maturation through class switch recombination and affinity maturation during disease progression in this inflamed non-lymphoid tissue. ### Competing Interest Statement M.D.R is a founder and consultant for TRex Bio., Sitryx Bio., Radera Bio, and Mozart Therapeutics.