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Identification and Characterization of Post-activated B Cells in Systemic Autoimmune Diseases
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- Weissenberg, Sarah Y. (författare)
- Charite Univ Med Berlin, Dept Rheumatol & Clin Immunol, Berlin, Germany; German Rheumatism Res Ctr Berlin DRFZ, Berlin, Germany
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- Szelinski, Franziska (författare)
- Charite Univ Med Berlin, Dept Rheumatol & Clin Immunol, Berlin, Germany; German Rheumatism Res Ctr Berlin DRFZ, Berlin, Germany
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- Schrezenmeier, Eva (författare)
- Charite Univ Med Berlin, Dept Rheumatol & Clin Immunol, Berlin, Germany
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- Stefanski, Ana-Luisa (författare)
- Charite Univ Med Berlin, Dept Rheumatol & Clin Immunol, Berlin, Germany
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- Wiedemann, Annika (författare)
- Charite Univ Med Berlin, Dept Rheumatol & Clin Immunol, Berlin, Germany
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- Rincon-Arevalo, Hector (författare)
- Charite Univ Med Berlin, Dept Rheumatol & Clin Immunol, Berlin, Germany; German Rheumatism Res Ctr Berlin DRFZ, Berlin, Germany; Univ Antioquia UdeA, Fac Med, Inst Invest Med, Grp Inmunol Celular & Inmunogenet, Medellin, Colombia
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- Welle, Anna (författare)
- Saarland Univ, Dept Genet & Epigenet, Saarbrucken, Germany
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- Jungmann, Annemarie (författare)
- Saarland Univ, Dept Genet & Epigenet, Saarbrucken, Germany
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- Nordström, Karl (författare)
- Saarland Univ, Dept Genet & Epigenet, Saarbrucken, Germany
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- Walter, Jörn (författare)
- Saarland Univ, Dept Genet & Epigenet, Saarbrucken, Germany
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- Imgenberg-Kreuz, Juliana (författare)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Reumatologi
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- Nordmark, Gunnel (författare)
- Uppsala universitet,Reumatologi,Science for Life Laboratory, SciLifeLab
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- Rönnblom, Lars (författare)
- Uppsala universitet,Reumatologi,Science for Life Laboratory, SciLifeLab,Rheumatology
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- Bachali, Prathyusha (författare)
- RILITE Res Inst, Charlottesville, VA USA
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- Catalina, Michelle D. (författare)
- RILITE Res Inst, Charlottesville, VA USA
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- Grammer, Amrie C. (författare)
- RILITE Res Inst, Charlottesville, VA USA
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- Lipsky, Peter E. (författare)
- RILITE Res Inst, Charlottesville, VA USA
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- Lino, Andreia C. (författare)
- Charite Univ Med Berlin, Dept Rheumatol & Clin Immunol, Berlin, Germany; German Rheumatism Res Ctr Berlin DRFZ, Berlin, Germany
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- Dörner, Thomas (författare)
- Charite Univ Med Berlin, Dept Rheumatol & Clin Immunol, Berlin, Germany; German Rheumatism Res Ctr Berlin DRFZ, Berlin, Germany
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(creator_code:org_t)
- 2019-09-24
- 2019
- Engelska.
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Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 10
- Relaterad länk:
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https://doi.org/10.3...
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https://uu.diva-port... (primary) (Raw object)
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https://www.frontier...
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https://urn.kb.se/re...
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https://doi.org/10.3...
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Abstract
Ämnesord
Stäng
- Autoimmune diseases (AID) such as systemic lupus erythematosus (SLE), primary Sjogren'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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Reumatologi och inflammation (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Rheumatology and Autoimmunity (hsv//eng)
Nyckelord
- systemic lupus erythematosus
- rheumatoid arthritis
- primary Sjogren's syndrome
- B cell receptor signaling
- toll-like receptor 9
- CD40
- post-activation
- anergy
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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- Av författaren/redakt...
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Weissenberg, Sar ...
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Szelinski, Franz ...
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Schrezenmeier, E ...
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Stefanski, Ana-L ...
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Wiedemann, Annik ...
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Rincon-Arevalo, ...
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visa fler...
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Welle, Anna
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Jungmann, Annema ...
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Nordström, Karl
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Walter, Jörn
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Imgenberg-Kreuz, ...
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Nordmark, Gunnel
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Rönnblom, Lars
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Bachali, Prathyu ...
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Catalina, Michel ...
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Grammer, Amrie C ...
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Lipsky, Peter E.
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Lino, Andreia C.
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Dörner, Thomas
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