To B or not to memory B…That is the question


What’ has this post got to do with MS? Well perhaps not a lot…except to say that it is B cell week at the Charcot MS Meeting in Italy.

So it is apt that in the past week we have had a review of B cell function by some opinion leaders and we get a lot of pretty pictures..very pretty…and a set of facts, as usual…sadly with next to no usual:-(.

I was surprised, really surprised that memory B cells did not get a mention in the review. Perhaps, I should not be surprised. If we have have a quick review of the programme at the Charcot Foundation (click) and see what is being served up. The importance of memory B cells has still yet to gain traction. I wonder if the data is all considered to be pants or perhaps because memory B cells have yet to be discovered by the opinion leaders, it does not exist.

We will see what gets said and we can have a report on this.

Again MS research lags behind research in arthritis where they showed years before MS that disease responds to CD20 B cell depletion…or is it CD20 T cell depletion, if we want to may complicated explanations. Personally I think this is a sad state of affairs It is one thing to argue rationally against a hypothesis you have issues with, but to ignore something obvious that you dare not talk about because you didn’t describe it…is perhaps pathetic. People continue to squirm when they talk about how ocrelizumab may work in MS, less they upset the T cell immunology labs.

The importance of memory B cell subsets have increasingly been recognised in other conditions. Even neuromyelitis optica (NMO) is ahead of MS. NMO is a spectrum of conditions associated with antibodies and spinal cord and optic nerve demyelination.. One variant has antibodies against myelin (Myelin oligodendrocyte glycoprotein) and another against aquaporin 4 on astrocytes. How do they repond to rituixmab? Which depletes memory B cells but does not deplete the antibody producing cells.

In this study they report that people with MOG antibodoies relapse within a couple of months whilst blood memory cells are gone and compares this with aquaporin 4-related NMO were they had. It probably adds so confusion and it says memory B cell numbers in the blood may not be where the action is at. I would say we know this already, learn from the arthritis literature. If people thought memory Bs were important you would perhaps have more specific, hence safer, B cell therapies by now, rather than worrying about the dose of glatiramer acetate or making monomethyl fumarate prodrugs. Instead we run around the B cell space like headless chickens making anti BAFF (fail), anti APRIL (fail) anti CD19 success with infections and non-depleting BTK inhibitors (pass but not that good)

Comparison of the response to rituximab between MOG- and AQP4-antibody diseases. Durozard P, Rico A, Boutiere C, Maarouf A, Lacroix R, Cointe S, Fritz S, Brunet C, Pelletier J, Marignier R, Audoin B.Ann Neurol. 2019 Nov 14. doi: 10.1002/ana.25648. [Epub ahead of print]

OBJECTIVE:To compare response to rituximab (RTX) between adult patients positive for myelin oligodendrocyte glycoprotein (MOG) and aquaporin-4 (AQP4) antibodies.

METHODS:We prospectively studied adult patients with MOG or AQP4 antibodies who received RTX under an individualized dosing schedule adapted to the biological effect of RTX monitored by memory B-cell measurement. Memory B cells were counted monthly and when relapse occurred. The biological effect of RTX was considered significant with < 0.05% memory B cells in peripheral blood lymphocytes.

RESULTS:In 16 patients with MOG antibodies and 29 with AQP4 antibodies, mean follow-up was 19 (range 9-38) and 38 (13-79) months. Under RTX, 10 relapses occurred in 6/16 (37.5%) patients with MOG antibodies and 13 occurred in 7/29 (24%) with AQP4 antibodies. The median time of relapse after the most recent infusion was 2.6 (0.6-5.8) and 7 (0.8-13) months, respectively (p<0.001). Memory B cells had reemerged in 2 of 10 (20%) relapses in patients with MOG antibodies and 12 of 13 (92.5%) with AQP4 antibodies (p<0.001).

INTERPRETATION:In AQP4 antibody-associated disorder, relapse mostly occurs when the biological effect of RTX decreases, which argues for treatment efficacy. In MOG antibody-associated disorder, the efficacy of RTX is not constant because one third of patients showed relapse despite an effective biological effect of RTX. In this subpopulation, memory B-cell depletion was unable to prevent relapse, which was probably caused by different immunological mechanisms.

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    • Nope not invited, not even after ProfK offered my services….so offically snubbed.

      The Great and the Good will be winging their way in for a day, wheeled out for the masses and yours truely will be stuck at home, hoping that I could be stopped one more time by the Home Office as I travel through immigration.

      It seems my Gospel is….Saint Elsewhere and not by the Lake…….Maybe they don’t like Evangelists and are happier to be taught be atheists, agnostics, Saint Same Old Same Old, Don’t Rock the Boat Old. Maybe the response to this comment, is the real Reason I will be watching from afar:-(

      So I’m now crying in my spilt milk.

      • Why is there so much resistance to your theory concerning memory B cells? Are you the smelly kid that nobody wants to play with or is it because you call a turd a turd (and we all know they can’t be polished).

        What do your colleagues in immunology think? Personally, I’m starting to think they should be leading the charge against MS, not neurologists.

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