It seems like a very intriguing idea and theory (although of course I don't really have the knowledge to understand it to any depth).
Can I ask a few question to see if I have understood the general concept:
By this theory, would autoimmune reactions only occur with self antigens that contain one of these 50-odd common self proteins? So for example, if we take the case of autoantibodies to adrenergic receptors, according to this theory, does that imply that the adrenergic receptors must contain one of those 50 proteins?
And likewise, does the theory imply any self antigen which does not contain one of these 50 self proteins cannot become a target for an autoimmune reaction?
In this
video tutorial of how B cells respond to antigens, the video narrator says (at timecode 7:40) that:
Is this where the theory of autoimmunity yourself, Cambridge and Abrahams are proposing says that it can all go horribly wrong, and lead to an autoimmune state?
Is this where the theory says that instead of weeding out B cells that make antibodies to self, this weeding out mechanism can sometimes go wrong in the case of these specific 50 self proteins, due to the negative feedback loop that would normally do the wedding out being inadvertently turned into positive feedback loop, and thus disastrously promoting the production of B cells that make antibodies to self?
Is this unfortunate promotion of B cells that make antibodies to self seen as a one-off random accident, which once it occurs, creates a long lasting pool of such B cells by polyclonal expansion, and these B cells thereafter cause autoimmunity by their constant production of antibodies to self? In other words, after this unfortunate one-off random accident occurs, is it only the pool of B cells that causes and maintains the autoimmune state?
Or is the idea that under certain (perhaps unknown) conditions which predispose the body to a higher risk of developing autoimmunity, these random accidents of promotion of B cells making antibodies to self happen more frequently, and it is a continual stream of these accidents which underpins and maintains the autoimmune state?
And regarding conditions that increase the risk of triggering autoimmunity: are there any factors the theory might predict would increase the likelihood of the normal negative feedback loop being inadvertently turned into a positive loop, for these 50 self proteins?
I understand that there is a significant increase in autoimmune diseases worldwide, suggesting some environmental factors are playing a role in the triggering process. So possibly these factors are directly affecting the inadvertent conversion of a negative feedback loop into the positive one that the theory says triggers autoimmunity?