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Very over-simplified: You have a random library of many billions of cells each making a single unique antibody that was created via random combinatorial genetic shuffling early on. The ones that accidentally bind to your own natural proteins are filtered out by killing them before they leave the bone marrow, so the circulating cells remaining form a library that could only bind -foreign- proteins. When one of these foreign-binding-cells in the library actually binds a foreign protein this cell multiplies like crazy and eventually the clones secrete free floating versions of the antibodies that neutralize the protein it detected, some of these clones stick around in the bone marrow to form a long-term memory-library of previously activated antibodies.

There are actually two separate systems: the T cells and B cells. I recommend the very readable Lauren Sompayrac's "How the Immune System Works". Or google/wiki "clonal selection" and "VDJ recombination".




Also google "somatic hypermutation". That multiplication process for B cells is inexact, and introduces mutations into the DNA (and therefore structure) of its children. There's a process which indicates whether any of these new antibodies binds better than the original one, which becomes a new candidate for multiplying.

There's fairly recent technology to sequence these antibodies en masse, which gives you a whole load (~10^6) of these antibody DNA sequences. It's a fascinating and frustrating exercise to try and reconstruct the mutation history and families of related cells from this data.


Is there concern that those long-lived antibody clones become pathological themselves?


Yes and no. Yes in that some of the many billions of combinations of antibody genes can recognize self proteins, which is a problem. However, during maturation of B cells, the immune system has a mechanism for killing of those B cells which would produce anti-self antibodies before they mature. There are times when this fails to work--think Grave's Disease, many forms of lupus, alopecia, etc.

I think in the sense you are asking, though, is that any long-lived plasma cell or memory B cell that is active will probably not change to the extent that they would attack self. I don't know off the top of my head if there are examples of this, but I can't think of any.




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