Biology: Antibodies and DNA Rearrangement

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How can there be an infinite number of antibodies? Well, maybe the words infinite is a little bit of a stretch. But you know, if you think about it, there's like a whole lot of different possible chemicals out there and maybe like I said, infinite is a stretch, but there's a lot. So, how are we going to make a lot of antibodies? How are we going to make an unbelievable number of varieties in that V region of the antibody? Because, remember, that's what we're talking about. We have to have the V region of the antibody where we going to get the variability.
Well, let's take a look at a potential situation. Stop screaming, I know this is DNA. But DNA is really at the essence of making all proteins. And what I want to do is I want to talk bout the gene that's going to code for antibodies. And I want you to imagine that there are - see these sections marked V1, V2, V3? - I want you to imagine not that there are there of those V sections, but perhaps hundreds, maybe even thousands of those. Small sections of DNA called V regions which you can imagine are going to code for the variable portion of the antibody.
Now, we've also put in here, one single C region. There are probably more than one C region, but you're not going to have the variety of C regions that you will V because the C region is called the constant region for a reason. Constant region, C. And then we have to have a junction region. So this is DNA. And what you know about DNA, you know that DNA has a neutron and that is going to be junk, we're going to cut that out. So, what's going to happen here? Well, the first thing that is going to occur is we're going to - and this is when it gets very interesting. Think back to your lessons on DNA. What happens in DNA is - and by the way, just a quick review. This would be, with all these different genes that are going to code for similar materials - did you ever hear of gene families? You may want to link back and listen up on gene families. Because we're talking about a gene family here, just like we are with the different forms of alpha hemoglobin, etc. So, let's see what's going to happen here.
First thing that happens is - let's go cellular, nuclear. The first event that is going to happen is going to be a cellular event. The B cell is going to start its maturing. So, where are we going? We're going to the bone marrow. So, the B cell bumps into the bone marrow and it's no longer totipotent, it's going to be a B cell. So we start B cell maturity. So, the lymphocyte gets in there and it starts to be a B cell. What does that mean? What that means is we're going to start deleting sections of DNA.
Now, think back to the times when you were learning about DNA when you were just a mere fledgling in Biology, probably, and you remember hearing about something called transposons and retro-transposons, which are merely copies of DNA and moving it around, but you also realized that pieces of DNA were sometimes deleted and moved. And that happens in DNA. And this is one of those cases where it's not only occurring, but it's crucial. Because what we've done here is we will cut out and move regions around in this DNA. And if you take a look at what has happened here, is the J region has been moved over to the V-2 region.
So we now have put this J over by the V-2. We've cut out and removed and probably broken apart digested V-3. We still have the intron and we still have the C. This is not mRNA. This is DNA. Don't get this confused. We're not doing any RNA work here yet. We're still in the nucleus. Well then, still in the nucleus, we're going to get our RNA transcript, or our pre-RNA transcript. And in the nucleus, we're going to make that pre-mRNA and look what we're going to do. Now we're going to transcribe from here through here. And now we have pre-mRNA. And now that we have made our pre-mRNA, notice what we've done. We've put this J over here in this variable region and that's going to become part of the variable region, but it's not bonding J to C. Remember the J region is going to be a junction, and that's what J is supposed to be all about. That's equal to a junction region. And it's going to joint J to C. So now we can do our typical mRNA editing. And we're going to have V-2, J, C. And then from that, we can make - so this is our mRNA - what would that make this? A protein. And so now what we have is by making several copies of this protein, we can make any number of this protein. And since we can make any number of this protein, perhaps hundreds of thousands of them? We can position them as regions and all it an antibody.
And so what we can literally do now is, and remember there's tertiary structures involved, there's the constant region, but the bottom line is this. What you are going to have right here is this whole idea of the variable region. And this variable region is what's going to recognize your antigen. And remember, proteins have very twisted structures. So this might look something like this. And this side would have the same configuration. And would only recognize an antigen that I can't draw, but would certainly probably fit right into that active site right there. Active site meaning that variable region right there. So, can we make an infinite number? I don't know about infinite, but let's think in numbers. Let's say hundreds of variables regions all arranged in that DNA, like so. Hundreds of them. And that you can cut them out, and you can arrange them any way you want. You can go 1,5; 1,4; 1,4,3,5; 1,4,3,2,5 - imagine hundreds of these. Now imagine the whole idea of transposons and retro-transposons and genetic variation. Can we make infinite numbers of antibodies? Nobody has ever counted. But, I haven't found yet a protein or an antigenic material that we don't have an antibody potential for. And that's very powerful and that's why we win the battle most of the time against those pathogens that are constantly trying to wreck our homeostasis, those nasty things.
Animal Systems and Homeostasis
The Immune System Continued
Antibodies and DNA Rearrangement Page [2 of 2]