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B Lymphocytes (B cells) : Overview of B cells (B lymphocytes) and how they are activated and produce antibodies
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- 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, 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
- 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?