{"entity": "publication", "iuid": "6e724d52a9404a59a893f520f63051f3", "timestamp": "2026-08-29T04:23:44.582Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/6e724d52a9404a59a893f520f63051f3.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/6e724d52a9404a59a893f520f63051f3"}}, "title": "Identification and Characterization of Post-activated B Cells in Systemic Autoimmune Diseases.", "authors": [{"family": "Wei\u00dfenberg", "given": "Sarah Y", "initials": "SY"}, {"family": "Szelinski", "given": "Franziska", "initials": "F"}, {"family": "Schrezenmeier", "given": "Eva", "initials": "E"}, {"family": "Stefanski", "given": "Ana-Luisa", "initials": "AL"}, {"family": "Wiedemann", "given": "Annika", "initials": "A"}, {"family": "Rincon-Arevalo", "given": "Hector", "initials": "H"}, {"family": "Welle", "given": "Anna", "initials": "A"}, {"family": "Jungmann", "given": "Annemarie", "initials": "A"}, {"family": "Nordstr\u00f6m", "given": "Karl", "initials": "K"}, {"family": "Walter", "given": "J\u00f6rn", "initials": "J"}, {"family": "Imgenberg-Kreuz", "given": "Juliana", "initials": "J"}, {"family": "Nordmark", "given": "Gunnel", "initials": "G"}, {"family": "R\u00f6nnblom", "given": "Lars", "initials": "L"}, {"family": "Bachali", "given": "Prathyusha", "initials": "P"}, {"family": "Catalina", "given": "Michelle D", "initials": "MD"}, {"family": "Grammer", "given": "Amrie C", "initials": "AC"}, {"family": "Lipsky", "given": "Peter E", "initials": "PE"}, {"family": "Lino", "given": "Andreia C", "initials": "AC"}, {"family": "D\u00f6rner", "given": "Thomas", "initials": "T"}], "type": "journal article", "published": "2019-09-24", "journal": {"title": "Front Immunol", "issn": "1664-3224", "volume": "10", "pages": "2136", "issn-l": "1664-3224"}, "abstract": "Autoimmune diseases (AID) such as systemic lupus erythematosus (SLE), primary Sj\u00f6gren's syndrome (pSS), and rheumatoid arthritis (RA) are chronic inflammatory diseases in which abnormalities of B cell function play a central role. Although it is widely accepted that autoimmune B cells are hyperactive in vivo, a full understanding of their functional status in AID has not been delineated. Here, we present a detailed analysis of the functional capabilities of AID B cells and dissect the mechanisms underlying altered B cell function. Upon BCR activation, decreased spleen tyrosine kinase (Syk) and Bruton's tyrosine kinase (Btk) phosphorylation was noted in AID memory B cells combined with constitutive co-localization of CD22 and protein tyrosine phosphatase (PTP) non-receptor type 6 (SHP-1) along with hyporesponsiveness to TLR9 signaling, a Syk-dependent response. Similar BCR hyporesponsiveness was also noted specifically in SLE CD27- B cells together with increased PTP activities and increased transcripts for PTPN2, PTPN11, PTPN22, PTPRC, and PTPRO in SLE B cells. Additional studies revealed that repetitive BCR stimulation of normal B cells can induce BCR hyporesponsiveness and that tissue-resident memory B cells from AID patients also exhibited decreased responsiveness immediately ex vivo, suggesting that the hyporesponsive status can be acquired by repeated exposure to autoantigen(s) in vivo. Functional studies to overcome B cell hyporesponsiveness revealed that CD40 co-stimulation increased BCR signaling, induced proliferation, and downregulated PTP expression (PTPN2, PTPN22, and receptor-type PTPs). The data support the conclusion that hyporesponsiveness of AID and especially SLE B cells results from chronic in vivo stimulation through the BCR without T cell help mediated by CD40-CD154 interaction and is manifested by decreased phosphorylation of BCR-related proximal signaling molecules and increased PTPs. The hyporesponsiveness of AID B cells is similar to a form of functional anergy.", "doi": "10.3389/fimmu.2019.02136", "pmid": "31616406", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC6768969"}], "notes": [], "created": "2026-08-21T12:58:45.600Z", "modified": "2026-08-21T12:58:45.614Z"}