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  1. Article ; Online: B cell subset distribution in human bone marrow is stable and similar in left and right femur

    Annika Wiedemann / Andreia C Lino / Thomas Dörner

    PLoS ONE, Vol 14, Iss 2, p e

    An instructive case.

    2019  Volume 0212525

    Abstract: The bone marrow (BM) is, in addition to being the site of B cell development, a tissue that harbors long-lived plasma cells (PC), the cells that protect the body against foreign antigens by continuous production of antibodies. Nothing is known about the ... ...

    Abstract The bone marrow (BM) is, in addition to being the site of B cell development, a tissue that harbors long-lived plasma cells (PC), the cells that protect the body against foreign antigens by continuous production of antibodies. Nothing is known about the long-term stability and functionality of both B cells and PC in the BM at the individual donor level since repeated sampling possibilities outside of oncology are scarce. Here, we had the opportunity to obtain BM samples from a patient undergoing bilateral total hip arthroplasty half a year apart. We observed that the frequencies of the analyzed B cell and PC subsets were similar despite a time of six months in between and sampling on left and right side of the body. Additionally, B cell receptor stimulation led to comparable results. Our data suggest that composition and functionality of B cells are stable in the BM of adults at the individual donor level.
    Keywords Medicine ; R ; Science ; Q
    Subject code 616
    Language English
    Publishing date 2019-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Therapeutic implications of the anergic/postactivated status of B cells in systemic lupus erythematosus

    Peter E Lipsky / Thomas Dörner / Franziska Szelinski / Andreia C Lino

    RMD Open, Vol 6, Iss

    2020  Volume 2

    Abstract: Systemic lupus erythematosus (SLE) is characterised by numerous abnormalities in B lineage cells, including increased CD27++ plasmablasts/plasma cells, atypical CD27-IgD- B cells with increased CD95, spleen tyrosine kinase (Syk)++, CXCR5- and CXCR5+ ... ...

    Abstract Systemic lupus erythematosus (SLE) is characterised by numerous abnormalities in B lineage cells, including increased CD27++ plasmablasts/plasma cells, atypical CD27-IgD- B cells with increased CD95, spleen tyrosine kinase (Syk)++, CXCR5- and CXCR5+ subsets and anergic CD11c+Tbet+ age-associated B cells. Most findings, together with preclinical lupus models, support the concept of B cell hyperactivity in SLE. However, it remains largely unknown whether these specific B cell subsets have pathogenic consequences and whether they provide relevant therapeutic targets. Recent findings indicate a global distortion of B cell functional capability, in which the entire repertoire of naïve and memory B cells in SLE exhibits an anergic or postactivated (APA) functional phenotype. The APA status of SLE B cells has some similarities to the functional derangement of lupus T cells. APA B cells are characterised by reduced global cytokine production, diminished B cell receptor (BCR) signalling with decreased Syk and Bruton’s tyrosine kinase phosphorylation related to repeated in vivo BCR stimulation as well as hyporesponsiveness to toll-like receptor 9 engagement, but intact CD40 signalling. This APA status was related to constitutive co-localisation of CD22 linked to phosphatase SHP-1 and increased overall protein phosphatase activities. Notably, CD40 co-stimulation could revert this APA status and restore BCR signalling, downregulate protein tyrosine phosphatase transcription and promote B cell proliferation and differentiation. The APA status and their potential rescue by bystander help conveyed through CD40 stimulation not only provides insights into possible mechanisms of escape of autoreactive clones from negative selection but also into novel ways to target B cells therapeutically.
    Keywords Medicine ; R
    Subject code 610
    Language English
    Publishing date 2020-08-01T00:00:00Z
    Publisher BMJ Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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