Postactivated B cells in systemic lupus erythematosus: update on translational aspects and therapeutic considerations.

Schrezenmeier, Eva; Weißenberg, Sarah Y; Stefanski, Ana-Luisa; Szelinski, Franziska; Wiedemann, Annika; Lino, Andreia C; Dörner, Thomas (2019). Postactivated B cells in systemic lupus erythematosus: update on translational aspects and therapeutic considerations. Current opinion in rheumatology, 31(2), pp. 175-184. Wolters Kluwer Health 10.1097/BOR.0000000000000576

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PURPOSE OF REVIEW

This review summarizes recent insights and current understanding of the role of postactivated B cells in SLE and related pathogenic and potential therapeutic implications.

RECENT FINDING

B cells are considered key players in SLE and experience from various B-cell-targeted therapies underlines their clinical relevance. In the last years, new insights have been obtained on B-cell abnormalities within the complex pathophysiology of SLE. These insights involve a revised understanding of BCR signaling, that has been reported to be hyperresponsive in the past, but newer studies suggest a postactivation functiotype in terms of reduced BCR and TLR signaling. Despite comprehensive efforts to delineate B-cell abnormalities on assessing large-scale genomic, epigenomic and proteomic data, understanding functional impairments of cellular interactions and subcellular functions remains crucial. A recently identified enhanced protein tyrosine phosphatase (PTP) activity was found in relation to diminished BCR responses in SLE. This finding together with reduced cytokine production upon TLR9 activation appears to mark postactivated lupus B cells. Other studies identified increased PTP activity in line with a gain-of-function mutation of phosphatase PTPN22, one of the strongest SLE risk alleles. Improved understanding of these B cell abnormalities in SLE holds promise to gain further insights in mechanisms of autoimmunity and pave the way for selective therapies targeting key principles of chronic autoimmunity.

SUMMARY

SLE B cells (similar as previously described for lupus T cells) are characterized by a postactivation (exhausted) functiotype mandating consideration for innovative therapies.

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