The B Team implicate star cells (Astrocytytes) as important B cell factors

The B Team inmplicates astrocytes

B cells accumulate in the CNS during MS. What keeps them going?  In this study they find the astrocyte secrtetes factors that promote B cell survival.
Take a B cell out of its environment for a few days and you have a dead B cell. In contrast T cells last for much longer. 
The Canadians have got their act together and have assembled a team to examine B cell activity. They show that astrocytes secrete factors that promote B cell survival.
Touil H, Kobert A, Lebeurrier N, Rieger A, Saikali P, Lambert C, Fawaz L, Moore CS, Prat A, Gommerman J, Antel JP, Itoyama Y, Nakashima I, Bar-Or A; Canadian B Cell Team in MS.
J Neuroinflammation. 2018 Apr 19;15(1):114. 


The success of clinical trials of selective B cell depletion in patients with relapsing multiple sclerosis (MS) indicates B cells are important contributors to peripheral immune responses involved in the development of new relapses. Such B cell contribution to peripheral inflammation likely involves antibody-independent mechanisms. Of growing interest is the potential that B cells, within the MS central nervous system (CNS), may also contribute to the propagation of CNS-compartmentalized inflammation in progressive (non-relapsing) disease. B cells are known to persist in the inflamed MS CNS and are more recently described as concentrated in meningeal immune-cell aggregates, adjacent to the subpial cortical injury which has been associated with progressive disease. How B cells are fostered within the MS CNS and how they may contribute locally to the propagation of CNS-compartmentalized inflammation remain to be elucidated.


We considered whether activated human astrocytes might contribute to B cell survival and function through soluble factors. B cells from healthy controls (HC) and untreated MS patients were exposed to primary human astrocytes that were either maintained under basal culture conditions (non-activated) or pre-activated with standard inflammatory signals. B cell exposure to astrocytes included direct co-culture, co-culture in transwells, or exposure to astrocyte-conditioned medium. Following the different exposures, B cell survival and expression of T cell co-stimulatory molecules were assessed by flow cytometry, as was the ability of differentially exposed B cells to induce activation of T cells.


Secreted factors from both non-activated and activated human astrocytes robustly supported human B cell survival. Soluble products of pre-activated astrocytes also induced B cell upregulation of antigen-presenting cell machinery, and these B cells, in turn, were more efficient activators of T cells. Astrocyte-soluble factors could support survival and activation of B cell subsets implicated in MS, including memory B cells from patients with both relapsing and progressive forms of disease.


Our findings point to a potential mechanism whereby activated astrocytes in the inflamed MS CNS not only promote a B cell fostering environment, but also actively support the ability of B cells to contribute to the propagation of CNS-compartmentalized inflammation, now thought to play key roles in progressive disease.
The question is what are the factors that promote this B cell activity? This study didn’t report on their identity however,
They produce IL-6, Finally, astrocytes produce BAFF (B cell activating factor of the TNF family) and promote proliferation of B cells via cell-to-cell contact based on other studies.

About the author



Leave a Reply to luis fernando Cancel reply

  • "They produce IL-6, Finally, astrocytes produce BAFF (B cell activating factor of the TNF family) and promote proliferation of B cells via cell-to-cell contact based on other studies."

    For years I've said to my neurologist(s) and commented on this blof that you should look closer into IL-6.

    If you can't find the culprit (cause) for MS than go for the next thing: restrict the communiation (in this case via IL-6).
    We alsready have IL-6 inhibitors. To me it seems that the dosage might be the only critical thing as IL-6 is also relevant for other immune responses.

    I am so confident in this idea that I would agree to a treatment with anti-IL-6-ABs (Toclizumab and others). But all of my neurologists are chickens…

    • I don’t think they are chickens, they just follow what big Pharma and the regulatory agencies dictate.

    • How is the anti-IL-6 going to effectively get into the CNS to target the astrocytes/B cells?. We know that 99.9% of administered antibody does not get into the CNS.

  • "B cells that were pre-exposed in
    transwell to unstimulated astrocytes did not substantially
    enhance T cell proliferation; however, pre-exposure of B
    cells to stimulated astrocytes in transwell resulted in B
    cells that induced significantly greater T cell proliferative

    This suport the view that B cell act as antigen presenting cells

    Bad for the black swan 🙁


    • A wellington boot with MHC on it presents antigen…in the 1970s people wasted loads of time giving gamma interferon to all sorts of cells to show this, only to find in vivo they never express MHC class II.

      We know that B cells express MHC class II and CD80 and other costimulatory molecules so will they present antigen…..sure they can
      but is this their function?. Thats why we have macrophages and dendritic cells….

  • "The potential significance of B cell persistence in the
    MS CNS, including within meningeal immune-cell collections,
    is highlighted by the growing recognition that B
    cells may contribute to disease-relevant immune responses
    through mechanisms that extend beyond antibody
    production (reviewed in [26])."

    So much so for OCB relevance 🙁

    • They simply have not thought enough, we know that most MS treatments block attacks but don't touch OCB…eg. HSCT. This does not mean they are irrelevant

  • "If you can't find the culprit (cause) for MS than go for the next thing: restrict the communiation (in this case via IL-6)."

    astrocyte-mediated enhancement of B cell survival and
    activation was also not impacted with neutralization of IL-
    6 or IL-15 in the astrocyte supernatants (Additional file 3:
    Figure S2a-d)."


  • What's the fuss?
    The body does not know what caused the damage within the CNS, so it mobilizes B-cells to search for it. That's where OCBs come from. They are the manifestation of an ongoing investigation. Just like in AIS.

    • I wouldn't dismisss this in such a blasé way VV. OCB's are significant. How significant will be revealed soon 😉

    • Just finishing putting together a paper on this very subject All will be revealed soon, OCBs in MS are important in the development of damage/disability and also cognitive impairment.

    • A paper about the association of OCB+ patients with cortical lesions. Also, a hint that OCB+ patients have more active B-cells. Should we be surprised? More damage, more response to damage.

    • Wrong again, it's the OCBs contributing to disease progression, not disease progression increasing OCBs.

    • "it's the OCBs contributing to disease progression"

      Sorry, this is never implied in the paper above. Instead:

      "Our hypothesis is that the presence of OCB might be an epiphenomenon of the compartmentalized intrathecal (meningeal) B cell response, which has been suggested to be associated with increased subpial demyelination and neuronal damage, both hallmarks of more rapidly progressive disease"

      Epiphenomenon is a greek word, roughly meaning a "marker" of an event. These guys say that it's the intrathecal B cell response that lies beneath the positive OCB status. The bands themselves are just an indicator.

    • MD2 any ideas what these mysterious molecules are? I keep hearing about them in post after post…. smaller than IG, not complement or any known cytokine…. presumably nothing to do with wellington boots either MD? Although I do laugh every time I read that comment 🙂

    • "The bands are contributing to the damage long-term"

      Still unsupported. Your links only refer to B-cell neurotoxicity, which is hardly a surprise: B-cells and all plasma immune cells are called into CNS in order to restore homeostasis, that is to remove damaged cells and bring functionality back. How can they wipe out malfunctioning cells if they are not excited against them? So, B-cell neurotoxicity does not prove that B-cells act abnormally or that they are the first damaging agent.

    • Antibodies
      More than fifty years ago, it was observed that MS patients had an increased
      level of antibodies in CSF.44 Later on it became clear that this increased
      production of antibodies were oligoclonal in distribution, i e only a limited
      number of plasma cell clones are contributing to the increased levels of
      antibodies.45 A further development was the development of the IgG-index,
      which is an estimate of intrathecal IgG production,46 and today the
      demonstration of intrathecal IgG production is part of the clinical routine in
      establishing a diagnosis of MS. However, the specificity of these antibodies
      has not been established. Most of the oligoclonal antibodies present in the
      CSF are not directed to the major myelin components,47 and some
      controversy exists as to the importance of those that do exist.36 Additionally,
      intrathecal antibody production can be seen in a variety of conditions.48 At
      present it is unclear whether these antibodies are harmful, protective, neither
      or both. It has been demonstrated that patients with RRMS and SPMS have
      antibodies directed towards oligodendrocyte precursor cell lines, but only the
      SPMS patients had antibodies directed towards a neuronal cell line.49 This
      supports the idea that the concept of epitope spreading is important in MS.


      Surprisingly, antibody levels did not drop substantially, in spite of the severe CD4 T and B lymphopenia during the first several months posttransplant. Consistent with that, oligoclonal immunoglobulins in the cerebrospinal fluid of most multiple sclerosis patients treated with autologous transplantation did not disappear [3,37,38]. As the half life of IgM and IgA is only ~5 days and that of IgG only ~23 days [39], the antibodies detected in the sera of our patients were continuously produced, presumably by plasma cells generated pretransplant. Plasma cells are radiation-resistant and long-lived [40–42]. The persistent antibody production does not appear to require posttransplant exposure of patients to the cognate antigens. Tetanus IgG levels in the first posttransplant year remained stable, even though the patients were not vaccinated in the first year and natural exposure to tetanus toxin in developed countries is extremely unlikely [43]. However, it is unclear whether this applies to other autologous transplant settings. In three studies presenting tetanus antibody levels after autologous transplantation for malignancies, the levels appeared to drop between pretransplant and 1 year posttransplant [44–46].

      From the infectious disease point of view, the persistent production of antibodies by plasma cells generated before the autologous transplantation may be beneficial, as most frequent pathogens are likely encountered pretransplant. Unfortunately, from the point of view of autoimmune diseases caused by autoantibodies like pemphigus (anti-desmoglein) or Lambert–Eaton myasthenic syndrome (anti-voltage gated calcium channel), the persistent production of autoantibodies may be deleterious. This may not apply to systemic sclerosis or multiple sclerosis in which the role of autoantibodies is uncertain. It is unlikely that the diseases caused by autoantibodies would be cured by autologous transplantation. In contrast, allogeneic transplantation might cure such diseases as it is associated with graft-vs.-host plasma cell reaction [47–49]. However, attempts to treat such diseases with autologous transplantation may still be warranted for the following two reasons: First, contrary to our observation, in five of six systemic lupus patients, double-stranded DNA antibodies became undetectable after autologous transplantation [50]. Second, clinical improvement may occur even if the autoantibody thought to cause the disease persists. In two of two myasthenia gravis patients, symptoms markedly improved after high-dose chemotherapy in spite of persisting acetylcholine receptor antibodies [51].


    • Dear Annonie Mouse
      No, the molecules are yet to be identified, presumably they will be but I think we can rule out the Wellington boot at this time.

    • "How can they wipe out malfunctioning cells if they are not excited against them?"
      All will be revealed;-)
      "B-cells and all plasma immune cells are called into CNS in order to restore homeostasis, that is to remove damaged cells and bring functionality back."
      Strange then that in fact all the evidence shows they result in the reverse, producing a long-lasting dystrophic environment and degeneration.

    • "they result"
      This is circular reasoning: You use your belief that B-cells are to blame in order to justify that B-cells cause damage.

  • But back in 1999 it was shown that EBV, for example, could infect astrocytes, and NDG treated here on the blog (I think in February of this year) about a last study that obtained the same conclusion.
    Then an infected astrocyte can communicate with an infected B cell, maintaining its survival for the EBV cycle, or not?!

By MouseDoctor



Recent Posts

Recent Comments