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Immunol."],"abstract":"<jats:p>B- and T-lymphocyte attenuator (BTLA\/CD272) is an inhibitory checkpoint molecule expressed on T and B cells. Prior studies reported defective function of BTLA by T cells in patients with systemic lupus erythematosus (SLE), whereas nothing is known about its role on B cells in SLE, a disease with various B cell abnormalities. Peripheral blood mononuclear cells (PBMCs) from 23 healthy donors (HD) and 34 SLE patients were stained for BTLA and its expression on B cells was assessed. PBMCs or CD27<jats:sup>-<\/jats:sup>IgD<jats:sup>+<\/jats:sup> naive B cells were stimulated together with an activating anti-BTLA antibody or an inhibitor of spleen tyrosine kinase (SYK) and differentiation as well as the expression of activation markers CD71, PD-1 and CD86 were analyzed. Our phenotypic and functional studies revealed reduced BTLA expression on CD27<jats:sup>-<\/jats:sup>IgD<jats:sup>+<\/jats:sup> na\u00efve B cells from SLE patients (p=0.0017) related to anti-dsDNA antibody titers (p=0.0394) and SIGLEC-1\/CD169 expression on monocytes (p=0.0196), a type I interferon marker related to disease activity. BTLA engagement was found to control CpG\/TLR9 activation limiting plasmablast (p=0.0156) and B cell memory induction (p=0.0078) in normal B cells in contrast to other B cell activation pathways (CD40, BCR). These BTLA functions were impaired in SLE B cells. Inhibition of SYK was found to mimic the effects of BTLA activity <jats:italic>in vitro<\/jats:italic>. Thus, is it possible that reduced BTLA expression and function of CD27-IgD+ antigen- and T cell-inexperienced SLE B cells could be overcome by SYK inhibition which should be tested in future studies as potential therapeutic principle.<\/jats:p>","DOI":"10.3389\/fimmu.2021.667991","type":"journal-article","created":{"date-parts":[[2021,4,22]],"date-time":"2021-04-22T13:01:03Z","timestamp":1619096463000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":23,"title":["BTLA Expression and Function Are Impaired on SLE B Cells"],"prefix":"10.3389","volume":"12","author":[{"given":"Annika","family":"Wiedemann","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Lettau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah 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