" a stretch with at best computer simulations to back it"

I agree. One of my ex-PhD students is now a molecular biophysicist. She solves the structures of, ironically, transcription factor complexes using NMR and X-ray crystallography.

She uses computational methods, including (in effect) simulations a lot.

In her papers she, at best, in the Discussion, might suggest that specific cell biology experiments could be done to check out how relevant her structural biology findings may be.

Here you go, for the NCBI article. http://www.medicinabiomolecular.com....as/do-1706.pdf

interesting cause of vit deficiency, or its receptor, definitely needs more research

DavidHC, some thoughts:

"It doesn't seem to settle the issue [VDR ablation] either way, almost a technical way of saying we just don't know what's going on, but there's stuff happening. :)."

I could not have put it better myself :)

"B-cells are also affected by 1,25(OH)2D, demonstrating decreased immunoglobulin production, proliferation and differentiation, but increased apoptosis."

I think that this is OK. Most B cells are passive. They only get activated by encountering specific antigens made by pathogens, usually with assistance from helper T cells. Two things happen to activated B cells; they differentiate into passive memory cells which are "ready and waiting" for the next time that their specific pathogenic antigen is present - they then get activated - this is why vaccinations are effective.

Activated B cells also differentiate into plasma cells, which secrete specific antibodies, which deal with the pathogen. If both activated B cells and plasma cells persisted in the absence of their specific antigen there is a risk that they could mutate, leading to an autoimmune disease or a B cell cancer like multiple myeloma. Because of that they "commit suicide" - undergo apoptosis - it seems that Vitamin D/VDR has a role in this.

"Computer simulation is not enough."

Commented on elsewhere.

"this study seems to take it for granted that inhibiting the ongoing proliferation of activated B cells and inducing their apoptosis is beneficial."

See above.

"keeping an eye on my IgG and neutrophils, which I should mention have slightly gone down in the last few months - I have two blood samples over 3 months on that - and the reading was already on the lowest end of the acceptable range."

I don't know enough about the clinical side of things to say much about this - mrsD could well help.

Both D2 and D3 have to be activated by the liver and the kidneys, to work in humans. I personally think it will be many years yet before we know more details about this complex system of D metabolism. Many of the studies so far still use mice or rats.

actually its alot more complicated than that. B-cells have to mature from an immature b-cell, it first has to express, primary igm first, than it switches depending on the situation, to prevent autoimmunity, if the b-cell is autoreactive it is "destroyed" in bone marrow before full maturing, soemtimes it escapes this for unknown reason, and gets into your system, which is where it can get checked, if autoreactive, then it is wiped here as well. If it escapes all of these it can cause autoimmunity, however it should have the genetic changes before hand, for a specific antigen.T-cells is similar as well.
For cancer, it is usually the immature, or stem cell stages that will become myeloma or b-cell cancer, its almost always pre-cursor, cell which are primitive and display self-renewel. fully mature immune cells are less likely to become cancer. Theres also alot of checks and balances that go from immature "precursor to b-cells" which is why autoimmunity is very hard to study sometimes.

Thank you for that Neuroproblem. Among other things I am an immunologist but that part of my research is concerned with innate immunity (the complement system).

I realise that my post was somewhat simplified but I hope that I did not confuse anybody.

Two things that you wrote struck me:

"primary igm first, than it switches depending on the situation, to prevent autoimmunity [emphasis added]"

My understanding of heavy chain class switching (aka isotype switching) is that it is controlled by cytokines made by Th1, Th2 and Treg cells - as far as I know it does not involve autoimmunity - can you shed some light on this?

"For cancer, it is usually the immature, or stem cell stages that will become myeloma"

As I understand it, myeloma arises from transformation of plasma cells, usually in the bone marrow. I may be wrong but I do not think that plasma cells are "immature" in the B cell lineage. Would you like to comment on this?

cancer is a little wierd, the formation of meyloma, i tried finding it, the research is pretty murky, they know the true origin of a myeloma, but i guess because plasma cells are fully mature, it can be the cause of it. It also indicated the "cancer stem cells" are responsible for myeloma growth. When i "read up on" cancers, they usually derive from an immature cells, since cancer can be considered immature or primitive. i think your correct on this, but i found some interesting papers on myelomas.
it seems that it can be indirectly related, i mustve meant the cd4+T cyto toxic cells. My immunology is rusty, i took this class last spring, there was so much to cover, and couldnt fit everything in one semester. i vaguely remember you mentioned that your an immunologist.
i was reading up on Ankylosising spondylitis, it seems to involve T-cell(i assume the cytotoxic), it was when i developed some strange spinal stiffness and pain near my sacral joints a month or 2 ago.

Neuroproblem, I did a bit of an investigation of ankylosing spondylitis a while ago (one of my friends has been diagnosed with it).

A major risk factor for it is inheriting a Class I MHC allele (HLA-B27) - more than 90% of people with it have that allele. As you say, that suggests cytotoxic T cell involvement.

I hope that this helps you.

yes that is what ive believed it indicated, cytotoxic t-cell can be seen in autoimmunity, because thier t-cell receptor is designed to recoginze certain "protein: sequences, and some can escape all the checks and balances and attack your own tissue, ecezema, psoriasis, and other dermatitis is also part of this, but i think interesting that t-cells can do this, this maybe the reason why anti-histamines dont work. hopefully the OP,is reading the full article i posted.

Kiwi,

Thank you for your thoughts and the information. Much appreciated. And my apologies for the late reply. I went back to work, a number of other issues arose, and so I’ve had very little time. I’m trying to keep up with the forum and today I did what I could.

Anyway, I wanted to comment on a couple of things, or something in particular, even though we could speak about a number of issues raised. I’ve quoted/pasted the relevant bit below.

Here’s the issue/question: Why aren’t you/we connecting the two issues below. If, as the article maintains, 1,25 affects B-cells in the way noted, why can’t it be both good and bad so to speak? It caused apoptosis, sure, but it also decreases production of B-cells, etc. Perhaps that could explain my low neutrophils and IgG. I mean, most likely, or at least my suspicion is that I have some sort of infection, or simply bacteria being released from my intestine into my blood stream, and my low WBC, here the neutrophils, are dying off fighting the infection, or something along those lines. Anyway, just a thought, an idea. But this article does note that there is some immunosuppressive aspect to vitamin D, and the research seems to speak to this. If so, on some level, our good engineer might have a point, one which he clearly takes to an implausible and unsupported extreme.



"B-cells are also affected by 1,25(OH)2D, demonstrating decreased immunoglobulin production, proliferation and differentiation, but increased apoptosis."

I think that this is OK. Most B cells are passive. They only get activated by encountering specific antigens made by pathogens, usually with assistance from helper T cells. Two things happen to activated B cells; they differentiate into passive memory cells which are "ready and waiting" for the next time that their specific pathogenic antigen is present - they then get activated - this is why vaccinations are effective.

Activated B cells also differentiate into plasma cells, which secrete specific antibodies, which deal with the pathogen. If both activated B cells and plasma cells persisted in the absence of their specific antigen there is a risk that they could mutate, leading to an autoimmune disease or a B cell cancer like multiple myeloma. Because of that they "commit suicide" - undergo apoptosis - it seems that Vitamin D/VDR has a role in this.


"keeping an eye on my IgG and neutrophils, which I should mention have slightly gone down in the last few months - I have two blood samples over 3 months on that - and the reading was already on the lowest end of the acceptable range."

I don't know enough about the clinical side of things to say much about this - mrsD could well help.