Now we're going to review how all of this leads to antibody diversity and give you a brief foreshadowing of something that we're going to do in the next lecture to even further tweak the effectiveness of an antibody. If you will recall, one of the biggest sources of diversity is simply mixing and matching any of these heavy chains with any of the light ones. And what that means, of course, is that all of the different things you can do to the heavy chain times all of the different things you can do to any of the light chains, reminding you that you've got two different sets of chromosomes, one from mom and one from dad. And you can see just mixing and matching all of the little possibilities for different gene regions can give you a huge opportunity for diversity, right now. Now, but that's not all. Okay, if you will recall, in addition to being able to put any V with any J, we also had that region where we joined them using P nucleotide addition. And that's going to, again, translate into some more interesting diversity at the third loop. Even further, when you're fooling around in the junction on the heavy chain chain, you have the N nucleotide addition that you throw in, in the middle of the P nucleotide addition. And so this region, here, surrounding the D element, all contributes to a huge amount of diversity in that third loop. So far, however, we have been stuck with the diversity provided by the variable chain for loops one and two. And now we get to complicate that through something called somatic hypermutation. So what happens here, and this is going to happen in the lymph nodes, is that the regions that code for the loops, which I've put here, have very interesting process that may happen to them when the B cell hits the lymph node. If you'll recall, we put together this V and J region with a P nucleotide addition in this little grey part in the bone marrow, sent it out, and if this finds the right kind of antigen the cell will activate and divide. Well, one of the things that can also happen is that it can enter a region in the lymph nodes and do some mutation to the regions that code for the CDR loops. So just to put this in here for you, the variable pink region, remember, codes for the first two loops in approximately the locations that I've indicated here. The third loop, of course, is formed by the junction. So these three regions become susceptible to a very interesting form of mutation. And what you'll get is mutational events that occur, at random like any mutational event, except they tend to concentrate solely in the regions that code for the loops. So you can see here that the parts of the gene, the code for the constant region, don't change at all. But, interestingly enough, most of the parts of the genes that code for the variable don't either. The only genes that tend to mutate are those in the regions of the gene that will eventually specify the amino acids in the loop. So here is a reminder of what an antibody looks like. And so we're going to go back and look at those loops again at the ends of the arms. And so here we have the loops shown here for the light chain kind of lined up with the gene parts that produce them. And so you can see that mutations in this region will actually change the amino acid sequences in the loops that ordinarily are simply specified straight up by the variable region. And it also occurs in the loop 3 region as well. So here we have the three loops from the light chain from the antibody and you can kind of correlate them with the different parts of the gene that produce them. And we're going to look at this process again, but when we talk about it, it's called somatic hypermutation. And it refers to random changes, throw the dice, that are pretty much confined to the amino acid instructions for just the loops. Now this, not only happens on a light chain, it happens in the heavy chain as well. So do that I'm sort going to turn this thing upside down, the antibody upside down. And if you look at it, here, we can see that here is the D third loop lines up with the D region and the second and first loops, again, are also lined up. So it's the same deal here. You get mutations in these regions, in the region that codes for loop 3 and in 2 regions in the variable region that code for the loops of that variable region. And so what this means is we're going to introduce some additional variation into the binding region of that antibody. And then we're going to select for the best versions. So this process, again, occurs later on, and we will put it in context in the next lecture.