Tertiary Lymphoid Structures Sustain Cutaneous B cell Activity in Hidradenitis Suppurativa

Lowe, M. M.; Cohen, J. N.; Moss, M. I.; Clancy, S.; Adler, J.; Yates, A.; Naik, H. B.; Pauli, M.; Taylor, I.; McKay, A.; Harris, H.; Kim, E.; Hansen, S. L.; Rosenblum, M. D.; Moreau, J. M.

doi:10.1101/2023.02.14.528504

bioRxiv · 10.1101/2023.02.14.528504

Tertiary Lymphoid Structures Sustain Cutaneous B cell Activity in Hidradenitis Suppurativa

Lowe, M. M.·Cohen, J. N.·Moss, M. I.·Clancy, S.·Adler, J.·Yates, A.·Naik, H. B.·Pauli, M.·Taylor, I.·McKay, A.·Harris, H.·Kim, E.·Hansen, S. L.·Rosenblum, M. D.·Moreau, J. M.

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Abstract

Structured AbstractO_ST_ABSBackgroundC_ST_ABSHidradenitis 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. ObjectiveWe aimed to investigate the dynamics and microenvironmental interactions of B cells within cutaneous HS lesions. MethodsWe 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. ResultsOur 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. ConclusionOur 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.

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Lowe, M. M., Cohen, J. N., Moss, M. I., Clancy, S., Adler, J., Yates, A., Naik, H. B., Pauli, M., Taylor, I., McKay, A., Harris, H., Kim, E., Hansen, S. L., Rosenblum, M. D., Moreau, J. M.. 2023-02-15. Tertiary Lymphoid Structures Sustain Cutaneous B cell Activity in Hidradenitis Suppurativa. https://doi.org/10.1101/2023.02.14.528504

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