Before we launch into the specifics of gene rearrangement. We're going to take a quick overall look at the three genes that code for either the heavy or light chain peptides of immunoglobulin receptor in its either receptor or antibody form. I'm specifically presenting the human version and not drawing out all 30 or 40 variable leader regions or every D or diversity region show them in green. On the other hand, here in my owl with many peptide, I have a yarn model that shows the entire series for the kappa y chain gene. So, let me open it up, and here is the three prime end of the gene. You can see I've got a single constant than region. I got some J's, and then I have all 40 going more and more. All 40 variable leader regions. Notice that the variable leader regions end with some other colored structures and so do the J's. These will be important in bringing these two regions together. As we start into lecture five and we're getting deeper into exactly what goes on in here, it will be some of the hardest parts of this course. So, to keep you oriented, I would like to compare what's going on in this gene to the eventual product, the antibody. So, I hope you can get out a picture of the antibody either from your notes or from the picture you've run off and of course your outline. Now, the picture behind me shows two different genes for the light chain and one for the heavy, all on different chromosomes. The heavy chain gene codes for this part here, and the light chain genes code for the short part here and here, the ones that make up half of the arms. While there are two different genes for the light chain, the structures that they code for are quite similar. So, this model works for either kappa or lambda. So, when we do gene rearrangement, this strictly refers to what happens in the regions that code for these two parts of the antibody, the variable regions here and here. That is, they refer to the changes that put together the information to make the VJ joint here or the VDJ joint here. These are not the only changes to the DNA that take place to make an antibody. But they're the only ones that are referred to as gene rearrangement. The other changes have different names. The whole point is that a cell has to do this first one, the rearrangement correctly, or it basically stops right there in lies down and dies. So, the next thing we're going to look at is some of the signaling that's involved in this and how we put these things together. So, here we have three different chains, genes, the top two are for the light chain, the bottom is for the heavy chain. You can see that these are three different genes so that you have two different ways of coding for a light chain. Interestingly, while the genes look rather different the chain, when it's done will look pretty much the same in overall structure. The heavy chain gene is down here at the bottom, you can, we'll eventually see that this is of course going to make it much longer and multi domained constant region, but it turns out that the variable regions are going to be constructed from the original gene in very similar ways. A reminder, each of these genes is on a different chromosome. I think that's kind of interesting because as it turns out, there's going to be cross talk between these genes to let each other know how things are going with it. So, while they're on different chromosomes, it's quite possible that during development they're dragged next to each other to a common sight in the nucleus so that communication can occur. The other thing I want you to notice from this is, if you compare this diagram to a diagram of the lambda chain and say a mouse in, for example, a supplementary textbook or an online discussion, you're going to see that there are some differences particularly in the arrangement of the constant J regions. In this course, we're going to go with a human and I want you to make sure you don't get confused if you see a somewhat different version that refers to a different organism. Since we are deployed, you may recall that you should have one version of this from mom and one version of this from dad. So, in your functioning genome, you should have two lambda genes, two kappa genes, and two heavy genes. So, you'll have four different ways of making a light chain and two different options for making a heavy chain. That's going to be important because as it turns out the mechanism that we're going to get into is quite inefficient and often generates non-functional genes that make non-functional proteins. So, it's nice to know you have a couple of tries before you have to give up on a particular gene. Now, the other thing that's probably pretty obvious in this is that we have a number of repeated units. Anytime you have a repeated units in your genome, the numbers can vary from person to person. Which is to say, if I have 30 or more copies of this leader variable region, well, because of the way gene expression and duplication works, I might wind up expanding that and getting some more copies or deleting copies, or more to the point, I made have a copy that was had a mutation in it that made it no longer functional. While I didn't show you any examples of this in the drawings from the human, you may see in other sources the J regions in particular with this funky little thing on and it looks like a trident. It's the Greek letter phi and it indicates a region that while it's there is no longer functional because it's had some sort of mutation. Now, another thing is that I'm going to use the word region for the individual elements in here and gene for the overall collection. Many authors use gene families, say for this whole heavy gene. I like to reserve the term gene family for a collection of related genes. For example, you have a hemoglobin gene family that includes the discrete gene for the alpha, the beta, the various kinds of embryonic hemoglobin and fetal hemoglobin. So, you have a number of complete genes for hemoglobin. In this case, each individual sub gene is not a family of different functioning genes, it's one highly complex gene which we're going to use to select various elements of in order to code for the antibody.
