B Lymphocytes (B cells)

Overview of B cells (B lymphocytes) and how they are activated and produce antibodies

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?