B lymphocytes (B cells)

Let's just talk about the humoral response right now, that deals with B lymphocytes. So B lymphocytes or B cells-- let me do them in blue. So let's say that that is a B lymphocyte. It's a subset of white blood cells called lymphocytes. It comes from the bone marrow and that's where the-- well, the B comes from bursa of Fabricius, but we don't want to go into detail there. But they have all of these proteins on their surface. Actually, close to 10,000 of them. I get very excited about B cells and I'll tell you why in a second. It has all of these proteins on them that look something like this. I'll just draw a couple of them. These are actually protein complexes, you can kind of view them. They actually have four separate proteins on them and we can call these proteins membrane bound antibodies. And I'll talk a lot more about antibodies. You've probably heard the word. You have antibodies for such and such flu, or such and such virus, and we're going to talk more about that in the future, but antibodies are just proteins. They're often referred to as immunoglobulins. These are essentially equivalent words. Antibodies or immunoglobulins-- and they're really just proteins. Now, B cells have these on the surface of their membranes. These are membrane bound. Usually when people talk about antibodies, they're talking about free antibodies that are going to just be floating around like that. And I'm going to go into more detail on how those are produced. Now what's really, really, really, really, really interesting about these membrane bound antibodies and these B cells in particular is that a B cell has one type of membrane bound antibody on it . It's going to also have antibodies, but those antibodies are going to be different. So we'll focus on where they're different. Let me just draw them the same color first and then we'll focus on where they're different. These are both B cells. They both have these antibodies on them. The interesting thing is that from one B cell to another B cell, they have a variable part on this antibody that could take on a bunch of different forms. So this one might look like that and that. So these long-- I'll go into more detail on that. The fixed portion, you can imagine is green for any kind of antibody, and then there's a variable portion. So maybe this guy's variable portion is-- I'll do it in pink. And every one of the antibodies bound to his membrane are going to have that same variable portion. This different B cell is going to have different variable portions. So I'll do that in a different color. Maybe I'll do it in magenta. So his variable portions are going to be different. Now he has 10,000 of these on a surface and every one of these have the same variable portions, but they're all different from the variable portions on this B cell. There's actually 10 billion different combinations of variable portions. So the first question-- and I haven't even told you what the variable portions are good for-- is, how do that many different combinations arise? Obviously these proteins-- or maybe not so obviously-- all these proteins that are part of most cells are produced by the genes of that cell. So if I draw-- this is the nucleus. It's got DNA inside the nucleus. This guy has a nucleus. It's got DNA inside the nucleus. If these guys are both B cells and they're both coming from the same germ line, they're coming from the same, I guess, ancestry of cells, shouldn't they have the same DNA? If they do have the same DNA, why are the proteins that they're constructing different? How do they change? And this is why I find B cells-- and you'll see this is also true of T cells-- to be fascinating is, in their development, in their hematopoiesis-- that's just the development of these lymphocytes. At one stage in their development, there's just a lot of shuffling of the portion of their DNA that codes for here, for these parts of the protein. There's just a lot of shuffling that occurs. Most of when we talk about DNA, we really want to preserve the information, not have a lot of shuffling. But when these lymphocytes, when these B cells are maturing, at one stage of their maturation or their development, there's intentional reshuffling of the DNA that codes for this part and this part. And that's what leads to all of the diversity in the variable portions on these membrane bound immunoglobulins. And we're about to find out why there's that diversity. So there's tons of stuff that can infect your body. Viruses are are mutating and evolving and so are bacteria. You don't know what's going to enter your body. So what the immune system has done through B cells-- and we'll also see it through T cells-- it says, hey, let me just make a bunch of combinations of these things that can essentially bind to whatever I get to. So let's say that there's just some new virus that shows up, right? The world has never seen this virus before this B cell, it'll bump into this virus and this virus won't attach. Another B cell will bump into this virus and it won't attach. And maybe several thousands of B cells will bump into this virus and it won't attach, but since I have so many B cells having so many different combinations of these variable portions on these receptors, eventually one of these B cells is going to bond. Maybe it's this one. He's going to bond to part of the surface of this virus. It could also be to part of a surface of a new bacteria, or part of a surface for some foreign protein. And part of the surface that it binds on the bacteria-- so maybe it binds on that part of the bacteria-- this is called an epitope. So once this guy binds to some foreign pathogen-- and remember, the other B cells won't-- only the particular one that had the particular combination, one of the 10 to the 10th. And actually, there aren't 10 to the 10th combinations. During their development, they weed out all of the combinations that would bind to things that are essentially you, that there shouldn't be an immune response to. So we could say self-responding combinations weeded out. So there actually aren't 10 to the 10th, 10 billion combinations of these-- something smaller than that. You have to take out all the combinations that would have bound to your own cells, but there's still a super huge number of combinations that are very likely to bond, at least to some part of some pathogen of some virus or some bacteria. And as soon as one of these B cells binds, it says, hey guys, I'm the lucky guy who happens to fit exactly this brand new pathogen. He becomes activated after binding to the new pathogen. And I'm going to go into more detail in the future. In order to really become activated, you normally need help from helper T cells, but I don't want to confuse you in the video. So in this case, I'm going to assume that activation can only occur-- or that it just needs to respond, it just needs to essentially be triggered by binding with the pathogen. In most cases, you actually need the helper T cells as well. And we'll discuss why that's important. It's kind of a fail safe mechanism for your immune system. But once this guy gets activated, he's going to start cloning himself. He's going to say, look, I'm the guy that can match this virus here-- and so he's going to start cloning himself. He's going to start dividing and repeating himself. So there's just going to be multiple versions of this guy. So they all start to replicate and they also differentiate-- differentiate means they start taking particular roles. So there's two forms of differentiation. So many, many, many hundreds or thousands of these are going to be produced. And then some are going to become memory cells, which are essentially just B cells that stick around a long time with the perfect receptor on them, with the perfect variable portion of their receptor on them. So some will be memory cells and they're going to be in higher quantities than they were originally. So if if this guy invades our bodies 10 years in the future, they're going to have more of these guys around that are more likely to bump into them and start and get activated and then some of them are going to turn into effector cells. And effector cells are generally cells that actually do something. What the effector cells do is, they turn into antibody-- they turn into these effector B cells-- or sometimes they're called plasma cells. They're going to turn into antibody factories. And the antibodies they're going to produce are exactly this combination, the date that they originally had being membrane bound. So they're just going to start producing these antibodies that we talk about with the exact-- they're going to start spitting out these antibodies. They're going to start spitting out tons and tons of these proteins that are uniquely able to bind to the new pathogen, this new thing in question. So an activated effector cell will actually produce 2,000 antibodies a second. So you can imagine, if you have a lot of these, you're going to have all of a sudden a lot of antibodies floating around in your body and going into the body tissues. And the value of that and why this is the humoral system is, all of a sudden, you have all of these viruses that are infecting your system, but now you're producing all of these antibodies. The effector cells are these factories and so these specific antibodies will start bonding. So let me draw it like this. The specific antibodies will start bonding to these viruses and that has a couple of values to it. One is, it essentially tags them for pick up. Now phagocytosis-- this is called opsonization. When you tag molecules for pickup and you make them easier for phagocytes to eat them up, this is what-- antibodies are attaching and say, hey phagocytes, this is going to make it easier. You should pick up these guys in particular. It also might make these viruses hard to function. I have this big thing hanging off the side of it. It might be harder for them to infiltrate cells and the other thing is, on each of these antibodies you have two identical heavy chains and then two identical light chains. And then they have a very specific variable portion on each one and each of these branches can bond to the epitope on a virus. So you can imagine, what happens if this guy bonds to one epitope and this guy bonds to another virus? Then all of a sudden, these viruses are kind of glued together and that's even more efficient. They're not going to be able to do what they normally do. They're not going to be able to enter cell membranes and they're perfectly tagged. They've been opsonized so that phagocytes can come and eat them up. So we'll talk more about B cells in the future, but I just find it fascinating that there are that many combinations and they have enough combinations to really recognize almost anything that can exist in the fluids of our body, but we haven't solved all of the problems yet. We haven't solved the problem of what happens when things actually infiltrate cells or we have cancer cells? How do we kill cells that have clearly gone astray?