Plasma cells live for a long time in the CNS

Pollok K, Mothes R, Ulbricht C, Liebheit A, Gerken JD, Uhlmann S, Paul F, Niesner R, Radbruch H, Hauser AE. The chronically inflamed central nervous system provides niches for long-lived plasma cells. Acta Neuropathol Commun. 2017 Nov 25;5(1):88

Although oligoclonal bands in the cerebrospinal fluid have been a hallmark of multiple sclerosis diagnosis for over three decades, the role of antibody-secreting cells in multiple sclerosis remains unclear. T and B cells are critical for multiple sclerosis pathogenesis, but increasing evidence suggests that plasma cells also contribute, through secretion of autoantibodies. Long-lived plasma cells are known to drive various chronic inflammatory conditions as e.g. systemic lupus erythematosus, however, to what extent they are present in autoimmune central nervous system inflammation has not yet been investigated. (Who are they kidding…oh yes the referees) In brain biopsies from multiple sclerosis patients and other neurological diseases, we could detect non-proliferating plasma cells (CD138+Ki67-) in the parenchyma. Based on this finding, we hypothesized that long-lived plasma cells can persist in the central nervous system (CNS). In order to test this hypothesis, we adapted the multiple sclerosis mouse model experimental autoimmune encephalomyelitis to generate a B cell memory response. Plasma cells were found in the meninges and the parenchyma of the inflamed spinal cord, surrounded by tissue areas resembling survival niches for these cells, characterized by an up-regulation of chemokines (CXCL12), adhesion molecules (VCAM-1) and survival factors (APRIL and BAFF). In order to determine the lifetime of plasma cells in the chronically inflamed CNS, we labeled the DNA of proliferating cells with 5-ethynyl-2′-deoxyuridine (EdU). Up to five weeks later, we could detect EdU+ long-lived plasma cells in the murine (mouse) CNS. To our knowledge, this is the first study describing non-proliferating plasma cells directly in the target tissue of a chronic inflammation in humans, as well as the first evidence demonstrating the ability of plasma cells to persist in the CNS, and the ability of the chronically inflamed CNS tissue to promote this persistence. Hence, our results suggest that the CNS provides survival niches for long-lived plasma cells, similar to the niches found in other organs. Targeting these cells in the CNS offers new perspectives for treatment of chronic autoimmune neuroinflammatory diseases, especially in patients who do not respond to conventional therapies.

Plasma cells which produce antibody are often found in bone marrow and can live for years but you put them in cell culture and they are dead in a few days. This is because the cells survive in niches where they recieve survival factors from surrounding cells. In this study they track the presence of plasma cells over weeks in animals and suggest that plasma ells survive for some time. I guess we have thought this happens for some time and it is evident that many of the plasma cells in the CNS are not directed to myelin antigens.

The question is what are we going to do?

Have a read if you are interested

The problem here ,is the pictures show the random isolated plasma cell and not B cell follcles

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  • The question is what are we going to do?

    Could this be one answer

    Objectives To investigate whether bortezomib, a
    proteasome inhibitor approved for treatment of multiple
    myeloma, induces clinically relevant plasma cell (PC)
    depletion in patients with active, refractory systemic
    lupus erythematosus (SLE).
    Methods Twelve patients received a median of two
    (range 1–4) 21-day cycles of intravenous bortezomib
    (1.3 mg/m2) with the coadministration of dexamethasone
    (20 mg) for active SLE. Disease activity was assessed
    using the SLEDAI-2K score. Serum concentrations of
    anti–double-stranded DNA (anti-dsDNA) and vaccineinduced
    protective antibodies were monitored. Flow
    cytometry was performed to analyse peripheral blood
    B-cells, PCs and Siglec-1 expression on monocytes as
    surrogate marker for type-I interferon (IFN) activity.
    Results Upon proteasome inhibition, disease activity
    significantly declined and remained stable for 6 months
    on maintenance therapies. Nineteen treatment-emergent
    adverse events occurred and, although mostly mild to
    moderate, resulted in treatment discontinuation in seven
    patients. Serum antibody levels significantly declined,
    with greater reductions in anti-dsDNA (∼60%) than
    vaccine-induced protective antibody titres (∼30%).
    Bortezomib significantly reduced the numbers of
    peripheral blood and bone marrow PCs (∼50%),
    but their numbers increased between cycles. Siglec-1
    expression on monocytes significantly declined.
    Conclusions These findings identify proteasome
    inhibitors as a putative therapeutic option for patients
    with refractory SLE by targeting PCs and type-I IFN
    activity, but our results must be confirmed in controlled




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