The B cell bandwagon gains momentum

Every one is getting in on the B cell bandwagon. 

There is review after review. Many give a lot of facts, but limited real insight. However, they contain some pretty pictures that may help you understand B cell development.

Sospedra M. B cells in multiple sclerosis. Curr Opin Neurol. 2018 Apr 7. doi: 10.1097/WCO.000000000000563. [Epub ahead of print]


Although it is becoming increasingly clear that B cells play important roles in multiple sclerosis (MS) pathogenesis, it is incompletely understood how they contribute. The purpose of this review is to provide an overview of the current knowledge about B cells in MS taking into account MS heterogeneity.


The efficacy of B cell-depleting therapies has provided strong evidence for the involvement of these cells in MS pathogenesis. Although pathogenic antibodies were found in some MS patients, the observation that plasma cells and antibodies remain largely unchanged after B-cell depletion suggests that B cells are involved in MS by other mechanisms than antibody production.


MS is an autoimmune disease, in which T and B cells play a crucial role. B cells can be involved in MS by different mechanisms such as presentation of antigens to T cells, transport of antigens from tissues to secondary lymphoid organs, secretion of pro-inflammatory or anti-inflammatory cytokines and in a subgroup of patients also production of pathogenic antibodies. As several B-cell/antibody-directed therapies are available, it is important to understand how these different functions of B cells and antibodies vary among patients in order to identify which could benefit best from the different therapies
Forsthuber TG, Cimbora DM, Ratchford JN, Katz E, Stüve O.
Ther Adv Neurol Disord. 2018 Mar 21;11:1756286418761697. 
Increasing recognition of the role of B cells in the adaptive immune response makes B cells an important therapeutic target in autoimmunity. Numerous current and developmental immunotherapies target B cells for elimination through recognition of cell-surface proteins expressed specifically on B cells, in particular CD19 and CD20. Similarities and differences in the function and expression of these two molecules predict some shared, and some distinct, pharmacological effects of agents targeting CD19 versus CD20, potentially leading to differences in the clinical safety and efficacy of such agents. Here, we review current knowledge of CD19 and CD20 function and biology, survey current and developmental therapies that target these molecules, and discuss potential differences in elimination of B cells by drugs that target CD19 versus CD20, with particular focus on the central nervous system autoimmune diseases multiple sclerosis and neuromyelitis optica. 

However, there are still some diehards.

Kaskow BJ, Baecher-Allan C. Effector T Cells in Multiple Sclerosis. Cold Spring Harb Perspect Med. 2018 Apr 2;8(4). pii: a029025
Multiple sclerosis (MS) has long been considered a CD4 T-cell disease, primarily because of the findings that the strongest genetic risk for MS is the major histocompatibility complex (MHC) class II locus, and that T cells play a central role in directing the immune response. The importance that the T helper (Th)1 cytokine, interferon γ (IFN-γ), and the Th17 cytokine, interleukin (IL)-17, play in MS pathogenesis is indicated by recent clinical trial data by the enhanced presence of Th1/Th17 cells in central nervous system (CNS) tissue, cerebrospinal fluid (CSF), and blood, and by research on animal models of MS, such as experimental autoimmune encephalomyelitis (EAE). Although the majority of research on MS pathogenesis has centered on the role of effector CD4 T cells, accumulating data suggests that CD8 T cells may play a significant role in the human disease. In fact, in contrast to most animal models, the primary T cell found in the CNS in patients with MS, is the CD8 T cell. As patient-derived effector T cells are also resistant to mechanisms of dominant tolerance such as that induced by interaction with regulatory T cells (Tregs), their reduced response to regulation may also contribute to the unchecked effector T-cell activity in patients with MS. These concepts will be discussed below.

ProfG says “What is the pivotal piece of evidence that makes T-cells the central play in MS”

This sounds like a “What is EAE review?”, but they too stick the boot into [to criticize someone who is already in a difficult position]CD4 T cells position. Is it time for change?

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  • "MS is an autoimmune disease". Bias right from the beginning. MS is still of unknown etiology. The rest is noise.

    It is sad to see that this hype regarding B-cells, apart from copy-pasting dozens of MS hypes (interferons, oral therapies, BG-12, Campath, HSCT, Tysabri with nearly 200 casualties so far), is not based on some knew, irrefutable pathological observations on MS, but on clay statistical grounds like "The efficacy of B cell-depleting therapies". Where "efficacy" contains everything, but disability progression.

    Do you see the paradox?
    They say "T and B cells play a crucial role", but they can't prove anything about the role itself.

    They say "B cells can be involved in MS by different mechanisms", but they can't prove one single mechanism of involvement.

    No one can say, "hey, this is definitely a damage done by B-cells".

    • Excellent response VV.

      I agree MD that anyone early into their course of RRMS without any progression of MS with should get on the B-cell therapy bandwagon, which is treating a downstream chain of events or effect of MS. That is if B-cell therapies, in fact, do prevent transition for RRMS to SPMS, which has yet to be fully established.

      The largest elephant in the room is why is there only focus by influential "card carrying" neurologists on neuroinflammatory treatments in MS, when they are shown to do very little in terms of treatment in progressive MS? The argument that we will worsen to the same horrible endpoint but just maybe a little slower on neuroinflammatory agents is unacceptable.

      Dr. G claims there are over 1 million wheelchair users of the 2.5 million MS patients diagnosed (and surely hundreds of thousands more with progressive MS) yet not one effective treatment for improving function by remyelination, neurorestoration and neuroprotection for likely >50% of all MS patients.

      These influential "card-carrying" neurologists, MS Societies and governing bodies should be telling pharma that this is completely unacceptable but instead they have become part of the problem and not the solution in MS progression. Why would you bite the hand that feeds you?

  • So why has nice turned down Ocrelizumab sayimg theres no proof its better than the high efficacy drugs already approved? Are they also die hard t cell enthisiasts?

  • I am very mindful, in an earlier explanation of B cells, of the number (10ˆ11?) of different "flavours" of B cell. Such a huge number that, we were told, there might only be a dozen individuals of each type in the blood stream. First question – are CD19 and CD20 two such individuals?

    I think of these individuals as being "hunters" looking out for instances, through the physical shape of the molecule of a specific antigen. EBV finds favour. I have been taking that "shape confusion" between EBV and myelin accounts for the inflammatory attacks of RRMS.

    I have also been assuming that it is T cells that actually do the attacking.

    I'd love to be set straight…

    • If the t cells are doing the targeting it has to be cd8 t cells not cd4 as oligodendrocytes do not express MHC class II.

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