We have been making the case that memory B cells are a central player in the treatment target for all drugs in MS.
As we saw yesterday many people don't buy this idea (see below) or perhaps don't even know about this idea because they: (a) don't read the blog; (b) Don't read papers (c) cannot assimilate knowledge or (d) all of the above:-) or (e) I'm wrong.
Yesterday I was sad, because it confirmed what I wrote above.
So I want to put more meat on the idea
I was talking about B cells and the fact there were are more than one type of cell that make up the CD19 population.
Some didn't like my slide
You (at least one of you) said I was talking "jibberish" and it is unrelated to people with MS and it was more relevant to scientists and doctors.
I said "nonsense" because, it is important in understanding the choices that you may need to make.
Is the level pitched wrongly...the answer will be yes and perhaps no...however virtually every part of the post has been explained in the past and so look at the education posts to help you get up to speed.
If you look at alemtuzumab, the CD19 B cell population (in green below) is back to normal levels within 3 months. But alemtuzumab is still working years later...so it can't be the B cell? Can it?
This is the view if you see CD19 B cells as a single population as is usually portrayed.
So can it be the B cell?
Yes it can, because that repopulation is occurring because of immature and then mature (also called naive B cells) cell subsets come rushing out of the bone marrow to fill the space vacated by the lymphocytes that are killed. This masks the fact that memory B cells are being depleted long-term.
See our picture from Baker et al. 2017 (below). This is the pattern you see with rituximab, and HSCT so there is nothing special going on.
The blue (Total CD19+) is a composite response of the (green, pink and the baby blue). The antibody is given at 0 and 12 months and shows percentage change from baseline (-80 = 80% depletion)
This is the default pathway for B cell repopulation and will occur for all drugs that kill B cells. However, with HSCT and alemtuzumab, this occurs in the relative absence of effective T cell regulation by CD8 T cells and maybe CD4 T regs. The default pathway of T cells is the immediate repopulation comes from expansion of the memory cells, this is seen in humans and mice. There is nothing special going on.
Labels: Memory B cells