{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T01:51:53Z","timestamp":1760233913691,"version":"build-2065373602"},"reference-count":38,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2021,3,12]],"date-time":"2021-03-12T00:00:00Z","timestamp":1615507200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"GINOP","award":["GINOP-232-15-2016-00050"],"award-info":[{"award-number":["GINOP-232-15-2016-00050"]}]},{"name":"EFOP","award":["EFOP 361-16-2016-00004"],"award-info":[{"award-number":["EFOP 361-16-2016-00004"]}]},{"DOI":"10.13039\/501100009594","name":"University of P\u00e9cs","doi-asserted-by":"publisher","award":["PTE \u00c1OK-KA 2020\/10"],"award-info":[{"award-number":["PTE \u00c1OK-KA 2020\/10"]}],"id":[{"id":"10.13039\/501100009594","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Thematic Excellence Program 2020 - Institutional Excellence Sub-programme of the Ministry for Innovation and Technology in Hungary, within the framework of the second thematic pro-gramme of the University of P\u00e9cs","award":["TKP2020"],"award-info":[{"award-number":["TKP2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>B cell activation is an early event in the development of systemic sclerosis (SSc). The classical activation of B cells downstream of the B-cell receptor (BCR) involves the phosphatidylinositol-3 kinase (PI3K) pathway that integrates the effects of multiple co-stimulatory receptors. Our analysis of PI3K pathway associated molecules in peripheral blood B cells of early diffuse cutaneous SSc (dcSSc) patients showed altered mRNA expression of Toll-like receptor (TLR) homolog CD180, TLR4, complement component 3, IL-4 receptor and secreted phosphoprotein 1 (SPP1). Parallel to this, we found elevated basal SPP1 secretion in dcSSc B cells, but, with BCR + IL-4 receptor co-stimulation, we could not induce further secretion. CD180 stimulation alone resulted in NF-\u03baB activation in more B cells than CD180 + BCR co-stimulation both in dcSSc and healthy control (HC), but the co-engagement increased the phosphorylation of NF-\u03baB only in dcSSc B cells. Additionally, in contrast with HC B cells, the lower basal production of IL-10 by dcSSc B cells could not be elevated with CD180 stimulation. Furthermore, activation via CD180 increased the percentage of CD86+ switched memory (CD27+IgD\u2212) B cells in dcSSc compared to HC. Our results suggest that alternative B cell activation and CD180 dysfunction cause imbalance of regulatory mechanisms in dcSSc B cells.<\/jats:p>","DOI":"10.3390\/ijms22062877","type":"journal-article","created":{"date-parts":[[2021,3,12]],"date-time":"2021-03-12T11:56:55Z","timestamp":1615550215000},"page":"2877","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Analysis of PI3K Pathway Associated Molecules Reveals Dysregulated Innate and Adaptive Functions of B Cells in Early Diffuse Cutaneous Systemic Sclerosis"],"prefix":"10.3390","volume":"22","author":[{"given":"Di\u00e1na","family":"Simon","sequence":"first","affiliation":[{"name":"Clinical Center, Department of Immunology and Biotechnology, University of P\u00e9cs Medical School, H-7624 P\u00e9cs, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Szabina","family":"Erd\u0151-Bony\u00e1r","sequence":"additional","affiliation":[{"name":"Clinical Center, Department of Immunology and Biotechnology, University of P\u00e9cs Medical School, H-7624 P\u00e9cs, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Judit","family":"Rapp","sequence":"additional","affiliation":[{"name":"Clinical Center, Department of Immunology and Biotechnology, University of P\u00e9cs Medical School, H-7624 P\u00e9cs, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P\u00e9ter","family":"Balogh","sequence":"additional","affiliation":[{"name":"Clinical Center, Department of Immunology and Biotechnology, University of P\u00e9cs Medical School, H-7624 P\u00e9cs, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T\u00fcnde","family":"Minier","sequence":"additional","affiliation":[{"name":"Clinical Center, Department of Rheumatology and Immunology, University of P\u00e9cs Medical School, H-7632 P\u00e9cs, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriella","family":"Nagy","sequence":"additional","affiliation":[{"name":"Clinical Center, Department of Rheumatology and Immunology, University of P\u00e9cs Medical School, H-7632 P\u00e9cs, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L\u00e1szl\u00f3","family":"Czirj\u00e1k","sequence":"additional","affiliation":[{"name":"Clinical Center, Department of Rheumatology and Immunology, University of P\u00e9cs Medical School, H-7632 P\u00e9cs, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T\u00edmea","family":"Berki","sequence":"additional","affiliation":[{"name":"Clinical Center, Department of Immunology and Biotechnology, University of P\u00e9cs Medical School, H-7624 P\u00e9cs, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"137","DOI":"10.5301\/jsrd.5000249","article-title":"Pathogenesis of systemic sclerosis: Recent insights of molecular and cellular mechanisms and therapeutic opportunities","volume":"2","author":"Varga","year":"2017","journal-title":"J. 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