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CD24 Expression and B Cell Maturation Shows a Novel Link With Energy Metabolism

Discussion in 'Latest ME/CFS Research' started by msf, Nov 9, 2018.

  1. msf

    msf Senior Member

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    https://www.ncbi.nlm.nih.gov/pubmed/30405620

    CD24 expression on pro-B cells plays a role in B cell selection and development in the bone marrow. We previously detected higher CD24 expression and frequency within IgD+ naïve and memory B cells in patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) compared with age-matched healthy controls (HC). Here, we investigated the relationship between CD24 expression and B cell maturation. In vitrostimulation of isolated B cells in response to conventional agonists were used to follow the dynamics of CD24 positivity during proliferation and differentiation (or maturation). The relationship between CD24 expression to cycles of proliferation and metabolism in purified B cells from HC was also investigated using phospho-flow (phosphorylation of AMPK-pAMPK), 1proton nuclear magnetic resonance and Mitotracker Far-red (Mitochondrial mass-MM). In vitro, in the absence of stimulation, there was an increased percentage of CD24+ viable B cells in ME/CFS patients compared to HC (p < 0.05) following 5 days culture. Following stimulation with B cell agonists, percentage of CD24+B cells in both naïve and memory B cell populations decreased. P < 0.01). There was a negative relationship between percentage of CD24+B cells with MM (R2 = 0.76; p < 0.01), which was subsequently lost over sequential cycles of proliferation. There was a significant correlation between CD24 expression on B cells and the usage of glucose and secretion of lactate in vitro. Short term ligation of the B cell receptor with anti-IgM antibody significantly reduced the viability of CD24+ memory B cells compared to those cross-linked by anti-IgD or anti-IgG antibody. A clear difference was found between naïve and memory B cells with respect to CD24 expression and pAMPK, most notably a strong positive association in IgD+IgM+ memory B cells. In vitro findings confirmed dysregulation of CD24-expressing B cells from ME/CFS patients previously suggested by immunophenotype studies of B cells from peripheral blood. CD24-negative B cells underwent productive proliferation whereas CD24+ B cells were either unresponsive or susceptible to cell death upon BCR-engagement alone. We suggest that CD24 expression may reflect variations in energy metabolism on different B cell subsets.


    Good to see this model being fleshed out, it's been the best bet to explain the lactic acid problem since at least the time I wrote my blog post about it. Seems to actually have been done partly in the UK too!
     
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  2. msf

    msf Senior Member

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    Microarray analyses of prostate cancer cells suggested that CD24 had a role as a growth-promoting factor, which was downregulated when the enzyme adenosine monophosphate kinase (AMPK) was inactivated

    On this note, I've recently started working again, and since my feet still havent recovered fully from the DCA, I've been using Resveratrol (1 g in the mornings), an ampk activator, to successfully reduce the lactic acid build up, with seemingly no or little neurotoxicity (definitely much less than either DCA or ALA).
     
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  3. msf

    msf Senior Member

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    Increased expression of CD24 which we have described on IgD+ B cells in peripheral blood of ME/CFS patients could thus reflect abnormalities in maintaining appropriate ATP generation perhaps mediated through inappropriate activation of AMPK

    Hmm, seems a bit more complicated than I first thoufht, but while I'm waiting for someone to translate it for me, I'm gonna keep using the Resveratrol as its working!
     
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  4. msf

    msf Senior Member

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    When the smart people look at this can they explain why ampk seems to be activated and lactate is increased?
     
  5. ljimbo423

    ljimbo423 Senior Member

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    I haven't analyzed the study yet, so I can't clarify anything. I've been researching Resveratrol though and ordered some yesterday.

    The research I did was looking for connections of Resveratrol to lowering brain inflammation. I think Jarred Younger has made a strong case for brain inflammation causing many (most?) symptoms in CFS. He also found high levels of lactate in the brain. I think he said from activated microglia.

    I'm going to take my Resveratrol sublingually if it don't taste to bad, so I get better absorption. There seems to be many studies that show Resveratrol lowers neuro-inflammation. Here is a link to a search I did for studies.

    Great to hear you're back to work!!:thumbsup::thumbsup:
     
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  6. junkcrap50

    junkcrap50 Senior Member

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    Wasn't there someone on here who had a theory about CD24 and CFS, specifically (I think) Naviaux's Cell Danger Response? Maybe it connecting it to something else. Was it @nandixon ?
     
  7. msf

    msf Senior Member

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    Thanks! I hope some of the stuff I and others have been trying and talking about on this forum can help other people get there too.

    With Resveratrol, I would be interested if you manage to get a good effect on sleep with it. I am still using trazodone with it, so it's hard to say what effect it's having on this, if any.
     
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  8. ljimbo423

    ljimbo423 Senior Member

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    I will let you know after I've taken it for several days. I didn't know it could help with sleep. If it helps with sleep, that would be a welcome bonus!

    I am slowly but consistently improving with the help of A LOT of supplements and diet. Many of the supplements I have tried because I read about other people posting about their success with them.

    BCAA's are helping tremendously at a dose of 16 grams a day.

    I think they work by bypassing the PDH enzyme. They enter the krebs cycle after PDH, by creating Acetyl CoA and that directly feeds the krebs cycle. Improving the krebs cycle and ATP production like DCA does.
     
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  9. msf

    msf Senior Member

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    I meant it migtm help with sleep due to tlr4 inhibition, although I'm not sure that this occurs in astrocytes, or how much gets into the brain.

    Re BCCA, what symptoms does this improve?
     
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  10. raghav

    raghav Senior Member

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    @ljimbo423 What source of resveratrol are you using ?
     
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  11. ljimbo423

    ljimbo423 Senior Member

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    Mostly fatigue. That of coarse also helps a lot with brain fog because of the increase in energy, giving me higher levels of concentration.

    It has also decreased the length of time and intensity of PEM I get, very noticeably. At 16 grams a day it has almost completely stopped the flu-like flares I would get, that would last for 2 days.

    Making me feel like I had an actual flu. I have only had 1 flu-like flare in about 4 months at that dose.

    If I had to put a percentage on how much my energy has increased from BCAA's, at 16-17 grams a day, I would say about 20-25%!

    Out of all the many dozens of supplements I have tried or still take. High dose BCAA's are by FAR the most effective, hands down!!
     
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  12. ljimbo423

    ljimbo423 Senior Member

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    I haven't got the Resveratrol yet. I ordered it a couple of days ago and should have it by Tuesday. This is the one I ordered.
     
    raghav likes this.

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