@ Jonathan Edwards
When there is no adaptive response to an infectious agent will B cells still respond with antiibody production ad random?
The key distinction is between the generation of new B cells, each with a different antibody, and growing up of these B cells into clones of plasma cells that make enough antibody to have an effect in the bloodstream.
New B cells are produced at random every day of our lives. This does not change in the presence of infection. Infection cannot have any effect on the genesis of antibodies because there is no way of 'telling DNA what antibody to make'. So the immune system has to use what seems like a very wasteful process. It makes a billion new antibodies every day and hopes that maybe a handful of these may be just the ones needed to bind to any infection that happens along.
The system works because if any of these B cells happen to pick up a foreign protein binding to the antibody carried on their surface they immediately multiply to form maybe 100 cells, maybe 100,000 cells, each producing the antibody that sticks to the foreign protein. This is the 'response', which is quite distinct from the random antibody invention.
A reasonable analogy might be the way people write books. Regardless of whether or not anybody will ever publish them there are always millions of authors writing books they hope people will read. Every day a vast range of 'random' manuscripts are produced. Sadly, 99.99% of these never sell a single copy. For some the publisher just says no thanks - and the B cell dies in the bone marrow. For some the publisher says why not write a shorter book just using the first six chapters - that is called 'receptor editing' and the B cell has another chance. For some the publisher publishes and the books lie on the table by the door in Waterstone's but nobody buys. Within a month the B cell gets pulped. For the lucky few someone picks them up and reads and says 'wow, I must tell everyone about this, this is so-o-o timely and relevant to the world situation'. Millions of copies get sold.
So life-enhancing books get sold at the time when they are of interest.
But imagine that one of our random authors writes a book called 'Mein Kampf'. It lies on the table and people pick it up and say 'wow, this is so-o-o timely for us in Germany, it is the way to restore the health of our great nation'. Millions of copies are sold and the result is the catastrophe of war. That is how I view autoimmunity.
So the answer to the historians' eternal question of what causes a war is that human society is so complex that it is inherently unstable
from within. A particular set of circumstances within society itself can set off an unstoppable cascade of destruction. I see the immune system as very similar. It is a society of individual cells co-operating but also competing. It is complicated enough to be susceptible to the same internal instabilities.
