Now, we turn to the details of a white jeans and the production of light peptides. Here's where we're headed. Eventually, we need to produce a process message, we need to take that process message, and translate it into a peptide. We need to process that peptide, and we need to attach it to the heavy chain, which is shown here. Just as a little bit of orientation, these are the corresponding parts of the diagrams, that is, this is the variable on the upper diagram, and the variable on the antibody diagram, the joining region, and the constant region. So, with that in mind, let's get started. We're going to go through, and review some of the things that we did before on the development of B cells. But, basically, we're going to then look at how we finish up this whole process, and get Secreting Plasma Cells, but for now, we're just going to look at this stuff that goes on in the bone marrow at the top of this particular diagram, which I have enlarged in this section. So, we're going to look at how we go from the Hematopoietic Stem Cell to eventually a mature B Cell. We're going to start when the Hematopoietic Stem Cell receives signals to become differentiated the Iga to then the Lymphoid Cell, the egross, and then we're going to see it's going to go into a B cell lineage. Now, the first thing that this thing does is actually, produces a signaling molecule, so that the cells around can keep track of what's going on. This is an Alpha-Beta globulin, immunoglobulin, and in the cytoplasmic part down in here, you're going to have some things that are called ITAMs, for Immuno Tyracine Activation Motifs, and they're going to be places where we can stick on a phosphate. In doing that, initiate signaling to the interior, and this, of course, has more CD names like CD45, which you don't have to learn it, you just have to know that those immunologists are at it again. What happens though when this is in and begins, at least some kind of signaling processes, it lets the B cell know, that it's time to rearrange the heavy chain gene. Those signals are going to come back and forth from those fat cells that we looked at before. So, there's going to be crosstalk between the B cells and the supporting cells around them, and they're going to signal, and that signal is going to be transmitted through the interior by that immunoglobulin, Alpha immunoglobulin and Beta signaling motif. So, here's the heavy chain, we've seen this before. First, we put the D with a J, then we put the V with the D, and then we go through the transcription and processing. We'll put out first of all, something that just has the Mu chain. So, we're going to use this part from here to here, and we're going to put those two Mu chain here, and here, associated with the signaling molecules. Now, notice the funky little green things that are hooked up to this, this enables this receptor to signal. We haven't rearranged the light chains yet, so we don't have a full immunoglobulin signaling molecule. What we have to do is essentially, fake out the system. We put up some thing that are called Surrogate Light Chains. These light chains are to work with the Heavy Chain Gene to signal to all of those other supporting cells that this cell has made a productive rearrangement. Again, it has two chances to do that, and if it doesn't it's going to apoptose. So, producing this particular structure is critical to the survival of the cell, and likewise the signals that it will transmit from signaling molecules are also critical to the survival of the cell. Now, I haven't been able to rearrange my light chain genes yet. So, these little proteins here are coded for by genes that don't need to be arranged. They will be upregulated during the course of heavy chain rearrangement, so that when the heavy chain is properly or rearranged, it will pick them up take them to the surface, display them, and the next word gets back is, "Good job there with your rearranging. Now, you can go rearrange your light chain." So, again, we have two different possibilities to make a light chain gene. First, we try the Kappa one which is down here, and, of course, we have two shots at that. If that doesn't work, we have two shots at the Lambda. If none of those four produce a productive rearrangement, the cell must undergo apoptosis. However, if it does, we get something that looks like this. This is your classical portrayal of an immunoglobulin receptor. At this stage, the stellar is still quite immature, it has the heavy and light chains, but the heavy chain will just be the Mu. We will make any of the del. This cell is now going to undergo negative selection, which I'm going to talk about it as soon as I finish this review. The process then at this point, ironically, will be that if this cell cross-links any of its receptors, it will do so in response to antigens in the bone marrow, and it will undergo apoptosis. So, in the previous one it had to have signals come into continue. Once it has this immature receptor in the bone marrow, a signal from this signals it's finding self-antigen, and then it'll undergo apoptosis. This one now is an immature B cell, and if it survives this next process, then it will become a mature B cell, and it will make the D chain, and it will be released from the plasma with a mixture of M and D immunoglobulin receptors on its surface, but the M. So, here we have a review of this again. We started out with a Metapoetic Stem Cell, we got a Pro-B Cell, that's what you call a cell that has the immunoglobulin Alpha and Beta Armen, and is rearranging the heavy chain. If that is successful, you have a Pre-B Cell. You can see these people are not your friends, they're really giving you some kinds of terminology that's not helpful at all, and inherently confusing. When I refer to these two processes, I will make it pretty clear even if I use these terms, exactly what's going on at this particular point in development. But, a Pro-B Cell is the one that's rearranging the heavy chain gene, a Pre-B Cell is a rearranging the light chain gene, and an Immature B Cell is the one that is getting ready to leave the bone marrow after its check for negative selection. Finally, we hope to get Immature B Cell, that has both the M and D receptors on the surface, and we'll head into a new part of this lecture. Before we go on, I'm going to put this up, and this shows the two M chains of two different immunoglobulin receptors getting cross-linked, and in this case they're getting cross-linked in the bone marrow. This is a bad thing, because if these guys cross-link in the bone marrow, this suggests that they are binding to a self-antigen. That's something you don't want, if you make antibodies that bind to a self-antigen, they can promote an autoimmune response. So, before we let those B cells unleashed into the peripheral circulation to run around and look for trouble, we made sure that the only ones that get out are ones that cannot recognize, at least the antigens that are present in the bone marrow. So, this is the process that's called Negative Selection, and it's designed to remove what are called Self Reactive B Cells. Now, if you come up with a cell that that's done this, and it's got Kappa chain, sometimes they can stop, go back a little bit, and try Lambda instead. But, one way or the other, you're not going to let out a B cell that is capable of binding to an antigen that is seen in the bone marrow.
