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B lymphocytes (B cells)

Video transcript

but let's just talk about the humoral the humoral response right now that deals with B lymphocytes so B lymphocytes or B cells let me let me do them in blue B for blue so let's say that that is a B lymphocyte it's a white blood cell 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 versus four brittish's but we don't want to go to detail there but they have all of these proteins on their surface actually close to ten thousand of them it's actually ignitable I get very excited about B cells and I'll tell you why in a second so it has all of these proteins on them that look something like this I'll just draw a couple of them these proteins these actually 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 membrane brown antibodies so these right here are membrane membrane bound antibodies and I'll talk a lot more about antibodies you've probably heard the word and you know do 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 you can really just antibodies are just proteins sometimes they'll you know they'll they're often referred to as immunoglobulins immuno globulins teaching biology really stresses my the spelling part of my brain but these are essentially equivalent equivalent words antibodies or mean you go blue um you know globally globulin and they're really just proteins now b-cells have these on the surface on the surface of their membranes these are membrane bound and usually when people talk about antibodies they're talking about free antibodies that are going to be that are going to just be floating floating around like that and I'm going to go 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 each b-cell right each B so you know that's one b-cell and let me draw another b-cell here so let's say that this is another b-cell right here it's going to also have antibodies but those antibodies are going to be different so though and we'll focus on where they're different so let me just draw them the same color first and then we'll focus on where they're different so that's one antibody membrane bound that's another antibody membrane bound these are both b-cells they both have these antibodies on them now the interesting thing is is that from one b cell to another b cell they have a varial part variable part on this antibody that can take a bunch of different comments so this one might look like that and that and these are the so these long I'll go into more detail on that and like that that so the colors well I don't let me do it like let me do it the so there's the fixed portion you combine is just 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 bond to his membrane are going to have that same variable portion now but this different b-cell it's going to have different variable portions so I'll do that in a let me do it in a different color I mean I'll do it in magenta so his variable portions are going to be different are going to be different just like that 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 and there's actually there's actually ten billion different combinations of variable portions so there's 10 to the 10th or 10 billion combinations 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 are maybe not so obviously all the proteins that are part of most cells are produced by the genes of that cell so if I draw you know this is the nucleus it's got its 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 shouldn't they have the same DNA and if they do have the same DNA and I'll put a big question mark there if they do have the same DNA why are the proteins that they're constructing different how do they change and this is what why I find b-cells and you'll see this is also true of t-cells to be fascinating is in their development in in their hematopoiesis I always have trouble of pronouncing that word but 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 so in mode you know 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 are maturing at one stage of their maturation or of 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 immunoglobulin and we're about to find out why there's that diversity so there's tons of stuff that can infect your body you know there's you know all sort of viruses are mutating and evolving and so our bacteria you don't know what's going to enter your body so what the 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 let's say there's just some new virus that shows up right the world has never seen this virus before and you know this b-cell little bump into this virus and this virus won't attach and then 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 maybe it's this one and he's going to bond 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 surfaced for some foreign protein and the part of the surface set of brines on the bacteria so maybe it binds on you know that part of that bacteria this is called an epitope 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 ten to tenth and actually there aren't ten to tenth combinations during their development they weed out all of the combinations that would bind to things that are inside of your that that are essentially you that shouldn't be that there shouldn't be immune spots to so we could say self self responding combinations weeded out so there actually aren't ten to the tenth ten 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 they're still 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 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 this video so in this case I'm going to I'm going to assume that activation can only occur or that just needs to respond it just needs to essentially be triggered by binding with the pathogen but we'll see 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 so this is the activated guy he's going to start cloning himself he's going to he to say look I'm the guy that can match this this this this virus here and so he's going to start cloning himself he's going to start dividing and repeating himself so let me just so there's going to be multiple versions of this guy multiple versions of this guy and not only are there multiple versions of that guy so they have the receptor the membrane they have 10,000 of these I'm only drawing one or two on each membrane so they all start to replicate and they also differentiate differentiating means they start taking particular roles so there's two forms of differentiation so they can go into so you know many many many hundreds or thousands of these are going to be produced and then some are going to become memory cells memory cells which are essentially just cells B cells that stick around a long time with the perfect receptor on them with the perfect variable portion of their receptor on them let me draw a couple of them right there so that is a memory cell so that right there is a memory cell so some will be memory cells and they're going to be in higher quantities than they were originally so if there's 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 to effector cells and effector cells are generally cells that actually do something so effector cells effector cells and what the effector cells do is they turn into they turn into antibody they turn into these effector B cells or sometimes they're called plasma cells they're going to turn into into antibody factories and to body factories and the antibodies are going to produce our exact actually this this combination the day that was that they originally had being membrane-bound so they're just going to start producing these antibodies that we talked about with the exact so they're going to start spinning them out they're going to start spinning 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 to the new pathogen this new thing in question they're going to be they're uniquely able to bind 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 a humoral system is all of a sudden you have all of these viruses that are infecting your system 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 these specific antibodies will start bonding so let me draw it like this these specific antibodies let me the specific antibodies will start bonding to these viruses and that has a couple of values I'll just draw them like that I don't want to spend too much time drawing them but that has a couple of values to it what is it essentially tags them for pickup now phagocytosis this is called opsonization when you have let me write this down opsonization ops and i sation when you tag molecules for pickup and you make them easier for phagocytes to eat them up this is what this is just called opsonization these molecules are called ups and opsin ins but it's antibodies are attaching them says 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 now you have this big thing hanging off the side of it it might be harder for them to infiltrate cells and then the other thing is is that you have on each of these on each of these antibodies you have two identical heavy chains I'll draw it like that and then two identical light chains two identical light chains and then they have a very specific variable pore on each one and each of these branches can bond to the epitope 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 optimized 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 they're that many combinations and they have enough combinations to really recognize almost anything that can be 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 that how do we how do we kill cells that have have clearly gone astray
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