Professor Jo Cambridge en collega's lijken een belangrijke immunologische afwijking op het spoor.
CD24 is een marker die op specifieke B-cellen aangetroffen wordt, met name op
transitionele B-cellen, maar ook op pro-B-cellen, pre-B-cellen, immature B-cellen,
naïeve B-cellen en B-geheugencellen.
De naïeve B-cellen en B-geheugencellen van ME/CVS-patiënten
(diagnose op basis van de herziene (?) Canadese Consensus-criteria)
hebben een significant hogere 'expressie' van CD24,
met name op naïeve B-cellen en B-geheugencellen.
die na immunologische stimulatie sterk af lijkt te nemen.
De eerste bevinding van de studie komt overeen met die van een studie uit 2006.
Bij stimulatie van de B cel-receptor ondergingen de B-geheugencellen zonder CD-24 marker
de normale groeicyclus, terwijl de B-cellen met de CD-24 marker niet reageerden of afstierven.
Verhoogde expressie van CD24 lijkt gerelateerd te zijn aan verminderde energieproductie.
De omvang van de mitochondriale productiecapaciteit is verminderd, het glucoseverbruik en de
lactaatvorming is verhoogd, hetgeen een verschuiving naar anaerobe energieproductie impliceert.
Het hoe en waarom is niet nog helemaal duidelijk, maar het lijkt erop dat CD24+ en CD24-
B-geheugencellen.een verschillende stofwisseling (energieproductiemethode) gebruiken.
CD24 expression and B cell maturation shows a novel link with energy metabolism: potential implications for patients with Myalgic Encephalomyelitis / Chronic Fatigue Syndrome.
Front. Immunol. 2018. doi: 10.3389/fimmu.2018.02421.
Mensah FK, Armstrong CW, Reddy V, Bansal AS, Berkovitz S, Leandro M, Cambridge G.
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.
Keywords:
B cells, Chronic fatigue syndrome (CFS), CD24, IgM memory B cells,
Metabolism, differentiation, pAMPKα phosphorylated AMPKα
https://www.frontiersin.org/articles/10.3389/fimmu.2018.02421/pdf
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