Memory B cells for MS….It’s nowt to do with me


This is a review that is open access for you to read.. I feel abit airbrushed but hey

DiSano KD, Gilli F, Pachner AR. Memory B Cells in Multiple Sclerosis: Emerging Players in Disease Pathogenesis. Front Immunol. 2021 Jun 8;12:676686. doi: 10.3389/fimmu.2021.676686.

Multiple Sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system. Once thought to be primarily driven by T cells, B cells are emerging as central players in MS immunopathogenesis. Interest in multiple B cell phenotypes in MS expanded following the efficacy of B cell-depleting agents targeting CD20 in relapsing-remitting MS and inflammatory primary progressive MS patients. Interestingly, these therapies primarily target non-antibody secreting cells. Emerging studies seek to explore B cell functions beyond antibody-mediated roles, including cytokine production, antigen presentation, and ectopic follicle-like aggregate formation. Importantly, memory B cells (Bmem) are rising as a key B cell phenotype to investigate in MS due to their antigen-experience, increased lifespan, and rapid response to stimulation. Bmem display diverse effector functions including cytokine production, antigen presentation, and serving as antigen-experienced precursors to antibody-secreting cells. In this review, we explore the cellular and molecular processes involved in Bmem development, Bmem phenotypes, and effector functions. We then examine how these concepts may be applied to the potential role(s) of Bmem in MS pathogenesis. We investigate Bmem both within the periphery and inside the CNS compartment, focusing on Bmem phenotypes and proposed functions in MS and its animal models. Finally, we review how current immunomodulatory therapies, including B cell-directed therapies and other immunomodulatory therapies, modify Bmem and how this knowledge may be harnessed to direct therapeutic strategies in MS.

Not one menion of EBV so have they really got the big picture. FcrH4 is a subset of memory B cells. As for CD52 it has it expressed all along the B cell lineage, but there is less on plasma cells (ASC antibody secreting cells). This is a good thing as you could lose your past immunity. Highly relevant in COVID-19 era. The graph below is message not protein.

So PPMS is not left out here is a reviiew for you

The Role of B Cells in Primary Progressive Multiple Sclerosis.
Holloman JP, Axtell RC, Monson NL, Wu GF.Front Neurol. 2021 Jun 7;12:680581. doi: 10.3389/fneur.2021.680581. eCollection 2021.

The success of ocrelizumab in reducing confirmed disability accumulation in primary progressive multiple sclerosis (PPMS) via CD20-targeted depletion implicates B cells as causal agents in the pathogenesis of PPMS. This review explores the possible mechanisms by which B cells contribute to disease progression in PPMS, specifically exploring cytokine production, antigen presentation, and antibody synthesis. B cells may contribute to disease progression in PPMS through cytokine production, specifically GM-CSF and IL-6, which can drive naïve T-cell differentiation into pro-inflammatory Th1/Th17 cells. B cell production of the cytokine LT-α may induce follicular dendritic cell production of CXCL13 and lead indirectly to T and B cell infiltration into the CNS. In contrast, production of IL-10 by B cells likely induces an anti-inflammatory effect that may play a role in reducing neuroinflammation in PPMS. Therefore, reduced production of IL-10 may contribute to disease worsening. B cells are also capable of potent antigen presentation and may induce pro-inflammatory T-cell differentiation via cognate interactions. B cells may also contribute to disease activity via antibody synthesis, although it’s unlikely the benefit of ocrelizumab in PPMS occurs via antibody decrement. Finally, various B cell subsets likely promulgate pro- or anti-inflammatory effects in MS.

So no mention of smouldering lesions and here lies the problem. Read it an it seems like the same biology as relapsing MS. If true its the same treatment…OK you may want it in the CNS. I would argue you need to do something different.

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  • A bit of an off-topic question, I’ve seen an increase in B-cell posts on the blog. Does this mean more people are publishing B-cell studies? We are studying T and B cells, what are the other bits of the puzzle that we need to uncover and research?

    • I have been posting B cell posts because this reflects a research focus, but there are more B cell studies

    • No..b cells and t cells are it..b cells are more important because EBV takes them over..b cells accumulate in target organ…and then are apc..antigen presenting cells to t cells
      to enter brain…Pender’s therapy is to use cd8+ infusions to kill ebv directly…don’t know if it will work even as well as hsct..but if people relapse w/ his therapy you just do more infusions.

      “CD8+ T-cell deficiency is a feature of many chronic autoimmune diseases, including multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus..etc..etc…
      Autoimmunity is postulated to evolve in the following steps: (1) CD8+ T-cell deficiency, (2) primary EBV infection, (3) decreased CD8+ T-cell control of EBV, (4) increased EBV load and increased anti-EBV antibodies, (5) EBV infection in the target organ, (6) clonal expansion of EBV-infected autoreactive B cells in the target organ, (7) infiltration of autoreactive T cells into the target organ, and (8) development of ectopic lymphoid follicles in the target organ. It is also proposed that deprivation of sunlight and vitamin D at higher latitudes facilitates the development of autoimmune diseases by aggravating the CD8+ T-cell deficiency and thereby further impairing control of EBV. The hypothesis makes predictions which can be tested, including the prevention and successful treatment of chronic autoimmune diseases by controlling EBV infection.”

      This is paper is 9 years old..but his ebv theory started in 2003.

      • I spoke at length with Prof Pender, I dont buy his hypothesis….I would also argue the results of the trials have not been good enough either

        • “I dont buy his hypothesis…”

          Fair enough..but why not..?
          It seems too good to be true to me.

          First trial..had only 10 and the 3 who had the most
          ebv reactive cells…all improved. But in this new trial
          people improve…but if the theory is correct more should
          improve and they should improve more in disability.

  • Wouldn’t IL6 inhibitors be of any use in MS?

    I suppose that’s where the holistic approach comes In and helps reduce inflammation and looking after the gut microbes

    • yep probably…However I think cytokines are terrible targets becuase they are found in balances, block one something else swings into place

        • “Yes true. Slow the reason the cytokines are being released.”

          Keep b cells out of the t cells and no IL2 cytokines.

          “After the autoreactive T cells have been reactivated by EBV-infected autoreactive B cells, they produce cytokines such as interleukin-2 (IL2), interferon-γ (IFNγ) and tumour necrosis factor-β (TNFβ) and orchestrate an autoimmune attack on the target organ (Path 5) ”

          From Fig. 1 illustration in this paper…

  • “OK you may want it in the CNS. I would argue you need to do something different.”

    Something very different…I would agree…Hard to believe that a double/triple dose of ocrevus wraps up ppms

    This man was ppms 6 months to edss 7……8 years to edss 10…spent 2 years on ocrevus trial…

    ocrevus vs. placebo in ppms

  • Is it possible that during Ocrevus treatment if there is an infection, PlasmaBlasts and Plasmacells are on rise, which then when blood sample is taken, CD19+ gives higher percentage?

  • Thank you MD for the post, does CD20+ cover all memory B-cells? I remember seeing a different version of this chart the bar of CD20+ is just bit shorter. May I also ask how are Memory B-cell subtypes described? How do they differentiate from each other?

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