CD24 expression and B cell maturation shows a novel link with energy metabolism: potential implications for patients with ME/CFS, 2018, Mensah et al

Andy

Andy

Senior Member (Voting rights)
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 vitro stimulation 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
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Currently abstract only at moment at https://www.frontiersin.org/articles/10.3389/fimmu.2018.02421/abstract
 
I think this IiME blog by Jo Cambridge is about this study?
In the first data paper published by Fane from UCL, he described abnormal expression of a molecule on B cells (CD24).
‘New’ B cells exit the bone marrow in large numbers every day (10^9) before undergoing a complex cycle of differentiation and maturation to become mature memory B cells or commit to producing antibodies.
This whole process is coordinated by regulated cycles of growth, cell death and very precise interactions with other immune cell types and the environment.
Therefore, the study of B cells allows us to investigate the dynamics of possible disruptions in checkpoints or pathways which may be altered in disease and thus impact immune functioning.
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http://www.investinme.org/ce-blog-1...a2OpOl5i6Gi75zQs9yiIjhwbq93r0h0Nk0QhgGj90rx8c
 
Thanks for sharing, that was a bit easier to understand! So they concluded that the abnormal expression might be due to the patient b cells trying to function normally? Considering Ritux didnt show significant effect in phase 3, some sort of downstream adaptation makes some sense i guess.

Man all these abnormalities puzzles me.. That they can be so many and that were still in limbo trying to close in on the causative events. Can`t wait till someone figures it out
 
Marky said:
Thanks for sharing, that was a bit easier to understand! So they concluded that the abnormal expression might be due to the patient b cells trying to function normally? Considering Ritux didnt show significant effect in phase 3, some sort of downstream adaptation makes some sense i guess.

Man all these abnormalities puzzles me.. That they can be so many and that were still in limbo trying to close in on the causative events. Can`t wait till someone figures it out
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Is there anything working right in our M.E bodies??
 
If we are not producing enough ATP because of an impaired aerobic system (so we get 2 ATP instead of 36 for every oxygen molecule) then it makes sense that nothing in our bodies works properly.

It is like a fault in the generator supplying energy to a house. The fridge will work as long as the cooker isn't on, using the hoover will stop the TV and so on.
 
Mithriel said:
so we get 2 ATP instead of 36 for every oxygen molecule
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I think that should be ''for every glucose molecule''. I agree with the gist of your post - if we have a malfunctioning energy metabolism, it is likely to have effects everywhere, but I'm not sure it's quite as simple as 2 instead of 36.

If we only used glycolysis (which produces 2ATP and doesn't use oxygen), then presumably we wouldn't need to breathe! As I understand it, we bypass the use of glucose in the mitochondria to some extent by utilising fats and amino acids (from protein), so we still have some mitochondrial energy production which uses oxygen. And I think the suggestion is that glucose metabolism in the mitochondria is reduced rather than stopped altogether.
 
Yes, got it wrong. I know these things then I try to say it and get it upside down, ME brain. I don't think all our cells are affected, that is why we are all so different. If only 10% of cells in each system is affected then it will work fine until a demand is made on it where it will reach a limit quickly.

I have psoriasis, an autoimmune disease where the skin cells grow too quickly, but it only appears in patches. In MS, only some nerve cells are demyelinated even if the immune system wrongly attacks. Very possible this is happening in ME.

In type 1 diabetes, the entire pancreas is not attacked at once either. Strange when you think about it. It is only things like a peanut allergy which cause an overwhelming reaction of the immune system. I wish I could work as a researcher, there are so many questions I would like to answer.
 
I agree that ME is the body running in an " energy conservation mode". Low T3 would also point to this. Low magnesium/ calcium issues affects cellular pumps, and if ATP is involved in distress purnergic signalling it may compound issues.
How each person downregulates, and how this is modulated may be affected by gene expression ( and potentially epigenetic gene expression) - hence why manifestations are different and different things affect different people.
I think there will be a number of common pathways uncovered as science develops the " tools" needed to unpick things.
 
Interesting to see that this is the most viewed paper in the journal this year. It seems that people are interested in the science of ME after all.

strategist said:
Does anyone understand how these findings relate to ME/CFS?
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I think the point is that (1) there seems to be a shift in young B cell populations involving the marker CD24. (2) much of the paper is about CD24 being involved in diverting cells down one metabolic pathway rather than another. The implication as I see it is that if we are looking for some general metabolic shift in ME then maybe CD24 is a marker of how that is affecting the immune response.
 
There's that senescence thing popping up again (my para breaks) :

In the absence of stimulation, an increased frequency of viable CD24+ B cells was found in cultures from ME/CFS patients compared to healthy controls. This in vitro finding was in line with what we have reported in our previous ex vivo whole blood phenotype study (16).

Over sequential cycles of proliferation in response to T-independent stimulation of B cells from healthy donors, there was an incremental decrease in frequency of CD24+ B cells in both naïve and memory B cells, as defined by CD27, in parallel with naïve B cell differentiation. CD27 is a marker for memory B cells, both unswitched (IgD+CD27+) and switched (IgD-CD27+).

However, a small population of memory B cells which has lost CD27, has been identified and is thought to represent a late or exhausted memory B cell sub-population (26, 36).

Interestingly, CD24 retention after stimulation in non-proliferating (cycle 0) memory B cells was related to age in healthy controls, suggesting that continued expression of CD24 might act as an unresponsiveness/senescence-associated marker on memory B cells.
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Old B cells; old muscles etc :

https://www.s4me.info/threads/old-m...fatigue-syndrome-2018-pietrangelo-et-al.6393/
 
The study is trying to reveal a potential link between previous observations of altered metabolism and immune dysfunction in people with ME. The study examined nine people with ME/CFS (Canadian Consensus Criteria) and eight healthy controls with a median age of 33.

The paper says there was a significant correlation between CD24 expression on B cells and the usage of glucose and secretion of lactate in vitro.

“The dynamic nature of B cells is a good model to observe changes in energy demand, in which CD24 seems to play an important role,” said Fane Mensah.

“There was more CD24 expression on B cells in ME patients. More CD24 was associated with more glucose and less lactate, which may mean that more CD24 is associated with less glycolysis,” explained Dr Chris Armstrong.
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https://meaustralia.net/2018/11/14/...-immune-dysfunction-and-metabolism-in-me/amp/
 
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