LECTURE 3

B Cells and
Antibodies, 27
B cells and the antibodies they produce are part
of the adaptive immune system. This defence
evolves during our own lifetime to protect us
against invaders that we, personally, have never
encountered before.
B Cells and Antibodies
 B cells and the antibodies they produce are part of
the adaptive immune system. B cells must be
B Cells and activated before they can make antibodies.
Antibodies “Fail‐safe” mechanisms help prevent inappropriate
B cell activation, and the principle of clonal
selection ensures that only those B cells which
HEADS UP! make antibodies appropriate to defend against an
invader are mobilized. A “mix‐and‐match” scheme
is used to construct the genes that encode a B
cell’s antibodies, and during the course of an
attack, B cells can upgrade the antibodies they
produce to mount a more targeted defence
Lecture Contents
 INTRODUCTION 27
 THE B CELL RECEPTOR 27
 HOW THE BCR SIGNALS 29
 HOW B CELLS ARE ACTIVATED 30
• T‐cell dependent activation 30
• T cell‐independent activation 31
• The logic of B cell activation 31
• Polyclonal activation 31
 CLASS SWITCHING 32
 ANTIBODY CLASSES AND THEIR FUNCTIONS 32
• IgM antibodies 33
• IgG antibodies 34
• IgA antibodies 34
• IgE antibodies 35
 SOMATIC HYPERMUTATION 37
 B CELLS MAKE A CAREER CHOICE 37
Lecture
Objectives

• Identify various components, functions and immune

mechanisms of adaptive immunity (B Cells).
• Differentiate between antigens and epitopes.
• Describe the structure and function of antibodies and
distinguish between the different classes of antibodies.
 INTRODUCTION
• Adaptive immune system, is a system so adaptable that can protect the body from
any possible invader.
• The most important components of the adaptive immune system is the B cell.
• B cells are born in the bone marrow, where they are produced from stem cells.
• B cells select gene segments coding for the two proteins that make up their B cell
receptors which appears on the surface of the B cell.
• Antibody molecule is identical to the B cell receptor, except that it lacks the
protein sequences at the tip of the heavy chain which anchor the BCR to the outside
of the cell.
• Antibody molecule that are exported out of the B cell is free to travel around the
body to do its job.
 THE B CELL RECEPTOR

• The BCR is made up of two kinds of

proteins, the heavy chain (Hc) and the light
chain (Lc), and each of these proteins is
encoded by genes that are assembled from
gene segments.

• The finished heavy chain protein (as

mentioned in the first lecture) is assembled
by pasting together four separate gene
segments (V, D, J, and C).
• Immunologists call such a combination of gene
segments a productive rearrangement.
• The obtained chromosome from the productive
rearrangement is used to construct the Hc protein.
• This heavy chain protein is then transported to the cell
surface.
• The B cell proliferates for a bit, and then the light chain
begins to constructed with the same rules.
• The completed heavy and light chain proteins must fit
together properly to make a complete antibody.
 If the B cell fails to productively rearrange heavy and
light chains, or if the Hcs and Lcs don’t match up
correctly, the B cell commits suicide.

• Every mature B cell produces only one kind of BCR or

antibody, made up of only one kind of Hc and Lc.
• By using a mix and match strategy to make the final
Hc and Lc genes of each B cell, the receptors on
different B cells are so diverse that B cells can probably
recognize any organic molecule that could exist.
The complete B cell receptor has two
parts:

The Hc/Lc part outside the cell that

recognizes the antigen but can’t
signal, and Igα & Igβ proteins
associate with the heavy chain protein
and protrude into the inside of the cell
where it can signal to the nucleus.
HOW THE BCR SIGNALS

• The antigen that a given B cell’s receptors recognize is called

cognate antigen.
• The tiny region of the cognate antigen that a BCR binds to is
called its epitope.
• When the BCR recognizes the matching epitope, it sends a
signal to the nucleus of the B cell, where genes involved in
activating the B cell can be turned on or off.
First:

many BCRs must be

brought close together
(BCRs are clustered
)on the surface of the B
cell (crosslinked) when
they bind to an antigen
with multiple epitopes
or to epitopes on
individual antigens.

https://quizlet.com/42046441/bio221-ch-17-results-of-
antigen-antibody-binding-flash-cards/
The clustering of BCRs brings enough Igα and Igβ molecules together to
set off the chain reaction that sends the “BCR engaged” signal.

• Another receptor on the surface

of a B cell can play an important
role in signalling which can bind
to complement fragments that are
attached to an invader. This
receptor is called a co‐receptor
and its role is very important
during the initial stages of an
attack.
• Recognition of B cell’s
co‐receptor serves to make B
cells sensitive to antigens which
the innate system already has
identified as dangerous(page 30).
HOW B CELLS ARE ACTIVATED

• Naive or virgin B cells is the cells that have never been

activated by encountering their cognate antigen.
• Experienced B cells is the B cells that have encountered
their cognate antigen and have been activated.
There are two ways that naive B cells can be activated to
defend the body against invaders.
 T cell‐dependent activation
 T cell‐independent activation
T‐cell dependent activation
• This way of activation requires two signals.
• First is the clustering of the B cell’s
receptors and their associated signalling
molecules.
• Second is the co‐stimulatory signal
supplied by a helper T (Th) cell.
• The second signal involves interaction
between two proteins on the surface of the B
cell(CD40) and the Th cell(CD40L).
T cell‐independent activation

• It is very active to the most common invaders that have carbohydrates or fats
on their surface which is opposite to T cell‐dependent activation where Helper
T cells only recognize protein antigens.
• T cell‐independent activation is antigen specific: Only those B cells whose
receptors recognize the repeated epitope will be activated.
• To be fully activated and produce antibodies, a naive B cell must receive a
second signal by a Toll‐like receptors (TLRs )that express on B cell service .
• In this way B cell can be act directly after recognized repeated epitope
antigen and act faster in antibody response.
• Most B cells that are activated by this type of activation are found in the
spleen where it can mount a rapid defence against bacteria .
The logic of B cell activation

• The logic of that B cell activation require two signals to be

activated is to avoid the possibility of self‐reactive B cells;
where it can recognize our own molecules and cause
autoimmune disease.
• B cell activates only when there is real danger.
 It is an additional activation method to the two
previous ways where B cells can be activated by
an antigen, usually called a mitogen, binds to
molecules on the B cell surface that are not B cell
receptors, then BCRs associated with these
molecules also can be clustered and the result is
activation of B cells.
Polyclonal
activation Polyclonal activation of B cells by a mitogen is
an example of the immune system gone
wrong.
CLASS SWITCHING
https://www.youtube.com/watch?v=jPqb1_pE41g

Maturation of B cells can be divided into three steps:

Class switching; a B cell can change the class of
antibody it produces.
Somatic hypermutation; the rearranged genes for the B
cell receptor where it can mutate to increase the average
affinity of the BCRs for their cognate antigen.
Career decision; whether B cell becomes an antibody
factory (a plasma B cell) or a memory B cell.
Class switching

• Antibody class switching is controlled by the cytokines that B

cells encounter when switching takes place.
• Certain cytokines or combinations of cytokines influence B
cells to switch to one class or another.
• Examples:
Type of Cytokine’s at environment B cells switching

IL‐4 and IL‐5 IgM to IgE

IFN‐γ IgM to IgG3
Somatic hypermutation

• Naive B cell that is first activated produces mainly IgM

antibodies.
• B cells also can produce IgD antibodies, that represent a tiny
fraction of the circulating antibodies in a human and it is unclear
whether they perform any significant function in the immune
defense.
• Antibody’s class is determined by the constant (Fc) region of its
heavy chain.
To switch its class, B cells cut off the IgM constant region DNA and paste it on
one of the other constant regions (deleting the DNA in between).
The drawing depicted B cell switches from an IgM constant region to an IgG
constant region.

Because the constant region

that determines how the
antibody will function, in
class switching, the part of the
antibody that binds to the
antigen (the Fab region)
remains the same, while
changing will be in the
constant; Fc part, where the
antibody gets a new Fc
region.
ANTIBODY CLASSES AND THEIR
FUNCTIONS

Depending on the unique

There are four main structure of each
classes of antibodies: antibody's constant
IgM, IgA, IgG, and IgE. region, each class has
different function.
IgM antibodies
 IgM antibodies have a lifespan of only
about one day
Activated naive B cells are mainly make
IgM antibodies.
 Comparing with IgG antibody, IgM
antibody is like five IgG antibody
molecules all stuck together.
 IgM is the perfect “first antibody” to defend
against viral or bacterial infections.

 IgM antibodies can neutralize

viruses by binding to them and
preventing them from infecting cells.

 IgM antibodies can activate

the complement cascade
during early stages of infection
that call fixing complement.
Classical (antibody‐dependent) pathway

• C1 is a big complex of the complement proteins (about 30) that

can activate the complement cascade if two or more C1
complexes are brought close together and release the inhibitor
molecule that is bound to it.
• When an invader binds to an IgM antibody antigen‐binding
regions, C1 complexes can bind to the Fc regions of the
antibody.
• Because each IgM antibody has five Fc regions close together,
two C1 complexes can bind to the Fc regions of the same IgM
antibody, bringing the complexes close enough together to set off
the complement cascade.
This is a specific activation pathway in which
only those antigens that bind to the antibody
will be targeted for complement attack.

https://www.youtube.com/watch?v=2jjyiXq8toc&ab_channel=PhysioPat
hoPharmaco
IgG antibodies p34

 IgG antibodies called gamma globulins.

 IgG antibodies are the longest-lived antibody class about
three weeks.
 IgG can pass from the mother’s blood into fetus blood
through the placenta.
 IgG antibodies can neutralize viruses.
IgG antibodies come in several different
subclasses with different functions.

IgG1can help in opsonizing invaders for ingestion

by phagocytes that have receptors on their surfaces
which can bind to the Fc portion of IgG1 .
opsonizing invaders Ingestion by phagocytes
 IgG3 antibody can fix
complement proteins.
 IgG3 antibody are involved in
antibody‐dependent cellular
cytotoxicity (ADCC) that
stimulates NK cell to be a more
effective killer.

In ADCC, the NK cell does the

killing, while the antibody
identifies the target.
Antibody‐dependent cellular cytotoxicity (ADCC)
 IgA antibodies p34

• IgA is the most abundant antibody class in the human body.

• IgA is the main antibody class that guards the mucosal surfaces
of the body.
• About 80% of the B cells that are located beneath mucosal
surfaces produce IgA antibodies that include the digestive,
respiratory, and reproductive tracts.
• IgA antibodies can be secreted into the milk of nursing mothers
which can protect the baby from ingested pathogens.
IgA antibodies are like two IgG
molecules held together by a “clip.”

• Clip functions facilitates the transport of IgA antibodies across the

intestinal wall and out into the intestine.
• The unique structure of IgA antibodies makes it resistant to acids and
enzymes found in the digestive tract.
• Dimeric IgA antibodies with four Fab regions to bind antigens make it
good at collecting pathogens together into clumps that are large
enough to be swept out of the body with mucus or feces.
 IgE antibodies p35

IgE antibodies are produced during parasitic infection that

make it defend against parasites.

IgE antibodies can be produced in response to allergen(An

antigen cause an allergic reaction) causes allergies.

IgE causes anaphylactic shock.

Relationship of IgE and parasitic diseases
related to immunity?

https://www.quora.com/Wh
at-is-the-relationship-of-IgE-
and-parasitic-diseases-
related-to-immunity
Type 1 IgE-mediated https://dermnetnz.org/topics/im
hypersensitivity reaction munoglobulin-e-tests

pathway

Type 1 hypersensitivity reaction

 Anaphylactic shock
p35

https://www.youtube.com/watch?v=5Sn4bi3t7YE&ab_channel=AlilaMedicalMedia
https://www.youtube.com/watch?v=llZFx8n-WCQ&ab_channel=AlilaMedicalMedia

• Anaphylactic shock is caused by mast cells degranulating where IgE

antibodies have a role in.
• Mast cells are white blood cells that are located beneath all exposed
surfaces (e.g., beneath the skin or the mucosal barrier).
• They lived for a very long time as they can survive for years in tissues.
• Their function is protecting the body against infection by parasites, also
they can cause an allergic reaction, and in extreme cases, anaphylactic
shock.
• Mast cells store active chemicals(such as histamine) and have IgE
receptors on their surface that can bind to Fc region of IgE antibodies.
https://microbeonline.com/immunoglobulin-e-ige-antibodies/
How Anaphylactic
shock occur? p36

• IgE antibodies can be produced

on the first exposure response
to allergen(An antigen cause an
allergic reaction).
• Then mast cells that have IgE
receptors on their surface bind to
the Fc region of these IgE
antibodies ready to https://www.youtube.com/watch?v=2tmw9x2Ot_Q&ab_ch
degranulated. annel=Osmosis
• On a second exposure to the allergen, IgE
antibodies that are already bound to the
surfaces of mast cells can bind to the allergen
and crosslink many IgE molecules on the
mast cell surface, dragging the Fc receptors
together which leads to it sending a signal to
mast cells to degranulate.
• Mast cell granules increase capillary
permeability casing fluids to escape from the
capillaries into the tissue.
• Why you get a runny nose and watery eyes when you have an allergic
reaction?

• If the allergen spreads throughout the body

and triggers massive degranulation of mast
cells, this will cause a heart attack and
difficulty in breathing.
SOMATIC HYPERMUTATION p37

• Somatic hypermutation is a relatively late event in the maturation

of B cells.
• Somatic hypermutation makes changes in the antigen‐binding
region of a BCR with three possible outcomes: The affinity of the
antibody for its cognate antigen may remain unchanged, it may
increase, or it may decrease.
• The assistance of helper T cells is required for B cells somatic
hypermutation
• B cells that are activated without T cell help (e.g., in response to
carbohydrates on the surface of a bacterium) don’t undergo either
class switching or somatic hypermutation.
 In the final step of B cell maturation, B cell could
become plasma B cell that is a antibody factory, or a
memory B cell.

B CELLS Plasma cell usually travels to the spleen or back to the

MAKE A bone marrow and begins to produce the secreted form
of the BCR – the antibody molecule.
CAREER
CHOICE p37 Memory B cell is extremely important that it recalls
the first exposure to a pathogen and helps defend
the body against subsequent exposures( faster and
mor efficient).
Memory B cells are produced with the help of helper
T cell.
Learning
Outcome

Describe the main concepts, structures, functions, immune mechanisms and

development of adaptive immunity (B Cells and Antibodies).
 The muddiest point

• Students in each group discuss together Chapter 3

(Lecture 3) information and write notes on the most
unclear or most confusing element of lecture.
 Team

Instructors

Of Immunology
& Serology
course