What's the Difference?

B-
cells and T-cells
When the body is invaded by bacteria, a virus or parasites,
an immune alarm goes off, setting off a chain reaction of
cellular activity in the immune system. Macrophages or
other innate immune cells, such as basophils, dendritic
cells or neutrophils, may be deployed to help attack the
invading pathogen. Those cells often do the job, and the
invader is destroyed. But sometimes, when the body
needs a more sophisticated attack, it turns to its T-cells
and B-cells. These cells are the special ops of the immune
system—a line of defense that uses past behaviors and
interactions to learn to recognize specific foreign threats
and attack them when they reappear.

They may also play a critical role in the development and

treatment of cancer. T-cells, especially, are the focal point
for two emerging immunotherapy treatments: checkpoint
inhibitors, which have been federally approved to treat
multiple cancers, and CAR T-cell therapy, which is being
studied in clinical trials as a potential treatment for
cancers of the bloodstream, such as leukemia and
lymphoma.

How does the immune system work?

The immune system is made up of two armies of cells:
innate and acquired. Innate immune cells are the body's
first line of defense. They quickly respond to foreign cells
to fight infection, battle a virus or defend the body against
bacteria. Our acquired immunity—also called adaptive
immunity—uses T-cells and B-cells when invading
organisms slip through that first line. These cells take
longer to develop, because their behaviors evolve from
learned experiences, but they tend to live longer than
innate cells. Adaptive immune cells remember foreign
invaders after their first encounter and fight them off the
next time they enter the body. This is the fundamental
premise for how vaccines work—using a small, harmless
amount of protein from a disease to allow the immune
system to recognize that protein if the pathogen were to
invade the body.

B-cells and T-cells are also called lymphocytes. “There are

primary and secondary lymphoid organs involved in the
complex development of lymphocytes,” says Pamela
Crilley, DO, Chair of the Department of Medical Oncology
at Cancer Treatment Centers of America® (CTCA). “The
primary lymphoid tissues in the initial generation of B- and
T-lymphocytes are the bone marrow and the thymus.”

B-cells fight bacteria and viruses by making Y-shaped

proteins called antibodies, which are specific to each
pathogen and are able to lock onto the surface of an
invading cell and mark it for destruction by other immune
cells. B-lymphocytes and cancer have what may be
described as a love-hate relationship. For example, B-cells
sometimes inhibit tumor development by producing
antibodies that may attack cancer cells or oncogenic
viruses, such as human papillomavirus (HPV), which is
responsible for most cervical, anal, penile and other
reproductive cancers. Other times, regulatory B-cells may
release immune-suppressive cytokines that stifle an anti-
tumor response. Also, B-cells are far more likely than T-
cells to mutate into a liquid cancer such as chronic
lymphocytic leukemia (CLL) or B-cell lymphoma.

What do T-cells do?

There are two main types of T-cells: helper T-cells and
killer T-cells. Helper T-cells stimulate B-cells to make
antibodies and help killer cells develop. Killer T-cells
directly kill cells that have already been infected by a
foreign invader. T-cells also use cytokines as messenger
molecules to send chemical instructions to the rest of the
immune system to ramp up its response. Activating T-cells
against cancer cells is the basis behind checkpoint
inhibitors, a relatively new class of immunotherapy drugs
that have recently been federally approved to treat lung
cancer, melanoma and other difficult cancers. Cancer cells
often evade patrolling T-cells by sending signals that make
them seem harmless. Checkpoint inhibitors disrupt those
signals and prompt the T-cells to attack the cancer cells.

Researchers are also developing a technology called CART

therapy, in which T-cells are engineered to attack specific
cancer cells. In this potential treatment, which is still in
clinical trials, a patient’s T-cells are collected and
genetically engineered to produce chimeric antigen
receptors (CAR). This is designed to allow the T-cells to
recognize a specific protein on the tumor cells. These
engineered CAR T-cells are grown by the billions in the
laboratory and then infused into a patient’s body, where
the cells are designed to multiply and recognize the cancer
cells that express the specific protein. This technology,
also called adoptive cell transfer, is generating excitement
among researchers as a potential next-generation
immunotherapy treatment.

While both are critical to the body's defense against

disease and infection, T-cells and B-cells play very
different roles. CART therapy and checkpoint inhibitors
are examples of how researchers are using what they’ve
learned about T-cells specifically in developing new cancer
treatments. But as their differences and similarities show,
both types of immune cells employ important natural
defenses in helping the body fight cancer.
Adaptive immunity

Have you ever wondered how your recovery time for the
common cold, the flu, or small infections seems to get shorter
after you’ve been exposed and successfully recovered the first
time? The adaptive immune system, also called acquired
immunity, uses specific antigens to strategically mount an
immune response. Unlike the innate immune system, which
attacks only based on the identification of general threats, the
adaptive immunity is activated by exposure to pathogens, and
uses an immunological memory to learn about the threat and
enhance the immune response accordingly. The adaptive
immune response is much slower to respond to threats and
infections than the innate immune response, which is primed
and ready to fight at all times.

Cells of the adaptive immune system

Unlike the innate immune system, the adaptive immune system
relies on fewer types of cells to carry out its tasks: B cells and T
cells.
Both B cells and T cells are lymphocytes that are derived from
specific types of stem cells, called multipotent hematopoietic
stem cells, in the bone marrow. After they are made in the bone
marrow, they need to mature and become activated. Each type
of cell follows different paths to their final, mature forms.

B cells
After formation and maturation in the bone marrow (hence the
name “B cell”), the naive B cells move into the lymphatic system
to circulate throughout the body. In the lymphatic system, naive
B cells encounter an antigen, which starts the maturation
process for the B cell. B cells each have one of millions of
distinctive surface antigen-specific receptors that are inherent to
the organism’s DNA. For example, naive B cells express
antibodies on their cell surface, which can also be
called membrane-bound antibodies.

B cell and membrane-bound antibodies

When a naive B cell encounters an antigen that fits or matches
its membrane-bound antibody, it quickly divides in order to
become either a memory B cell or an effector B cell, which is also
called a plasma cell. Antibodies can bind to antigens directly.

Antigen binding to B cell antigen binding site

The antigen must effectively bind with a naive B cell’s
membrane-bound antibody in order to set off differentiation, or
the process of becoming one of the new forms of a B cell.

B cell differentiation process resulting in plasma cell and memory

B cell
Memory B cells express the same membrane-bound antibody as
the original naive B cell, or the “parent B cell”. Plasma B cells
produce the same antibody as the parent B cell, but they aren’t
membrane bound. Instead, plasma B cells can secrete
antibodies. Secreted antibodies work to identify free pathogens
that are circulating throughout the body. When the naive B cell
divides and differentiates, both plasma cells and memory B cells
are made.
B cells also express a specialized receptor, called the B cell
receptor (BCR). B cell receptors assist with antigen binding, as
well as internalization and processing of the antigen. B cell
receptors also play an important role in signaling pathways. After
the antigen is internalized and processed, the B cell can initiate
signaling pathways, such as cytokine release, 7 to communicate
with other cells of the immune system. For more information on
cell signalling, check out this article on cell-to-cell
communication.

T cells
Once formed in the bone marrow, T progenitor cells migrate to
the thymus (hence the name “T cell”) to mature and become T
cells. While in the thymus, the developing T cells start to
express T cell receptors (TCRs) and other receptors
called CD4 and CD8 receptors. All T cells express T cell receptors,
and either CD4 or CD8, not both. So, some T cells will express
CD4, and others will express CD8.
Unlike antibodies, which can bind to antigens directly, T cell
receptors can only recognize antigens that are bound to certain
receptor molecules, called Major Histocompatibility Complex
class 1 (MHCI) and class 2 (MHCII). These MHC molecules are
membrane-bound surface receptors on antigen-presenting cells,
like dendritic cells and macrophages. CD4 and CD8 play a role in
T cell recognition and activation by binding to either MHCI or
MHCII.

Macrophage binding to T cell

T cell receptors have to undergo a process called rearrangement,
causing the nearly limitless recombination of a gene that
expresses T cell receptors. The process of rearrangement allows
for a lot of binding diversity. This diversity could potentially lead
 to accidental attacks against self cells and molecules because
some rearrangement configurations can accidentally mimic a
person’s self molecules and proteins. Mature T cells should
recognize only foreign antigens combined with self-MHC
molecules in order to mount an appropriate immune response.

T cell positive selection and negative selection

In order to make sure T cells will perform properly once they
have matured and have been released from the thymus, they
undergo two selection processes:
1. Positive selection ensures MHC restriction by testing the ability
of MHCI and MHCII to distinguish between self and nonself
proteins. In order to pass the positive selection process, cells
must be capable of binding only self-MHC molecules. If these
cells bind nonself molecules instead of self-MHC molecules, they
fail the positive selection process and are eliminated by
apoptosis.
2. Negative selection tests for self tolerance. Negative selection
tests the binding capabilities of CD4 and CD8 specifically. The
ideal example of self tolerance is when a T cell will only bind to
self-MHC molecules presenting a foreign antigen. If a T cell binds,
via CD4 or CD8, a self-MHC molecule that isn’t presenting an
antigen, or a self-MHC molecule that presenting a self-antigen, it
will fail negative selection and be eliminated by apoptosis.
These two selection processes are put into place to protect your
own cells and tissues against your own immune response.
Without these selection processes, autoimmune diseases would
be much more common.

T cell positive selection and negative selection process

After positive and negative selection, we are left with three types
of mature T cells: Helper T cells (T\text{}_{H}Hstart text, end text,
 start subscript, H, end subscript cells), Cytotoxic T cells
(T\text{}_{C}Cstart text, end text, start subscript, C, end
subscript cells), and T regulatory cells (T\text{}_{reg}regstart text,
end text, start subscript, r, e, g, end subscript cells).
 Helper T cells express CD4, and help with the activation of
T\text{}_{C}Cstart text, end text, start subscript, C, end
subscript cells, B cells, and other immune cells.
 Cytotoxic T cells express CD8, and are responsible for removing
pathogens and infected host cells.
 T regulatory cells express CD4 and another receptor, called
CD25. T regulatory cells help distinguish between self and
nonself molecules, and by doing so, reduce the risk of
autoimmune diseases.

Helper T cell, Cytotoxic T cell, T regulatory cell diagrams

Humoral vs. Cell Mediated Immunity

Immunity refers to the ability of your immune system to defend
against infection and disease. There are two types of immunity
that the adaptive immune system provides, and they are
dependent on the functions of B and T cells, as described above.
Humoral immunity is immunity from serum antibodies produced
by plasma cells. More specifically, someone who has never been
exposed to a specific disease can gain humoral immunity
through administration of antibodies from someone who has
been exposed, and survived the same disease. “Humoral” refers
to the bodily fluids where these free-floating serum antibodies
bind to antigens and assist with elimination.
Cell-mediated immunity can be acquired through T cells from
someone who is immune to the target disease or infection. “Cell-
mediated” refers to the fact that the response is carried out by
cytotoxic cells. Much like humoral immunity, someone who has
not been exposed to a specific disease can gain cell-mediated
immunity through the administration of T\text{}_{H}Hstart text,
end text, start subscript, H, end subscript and T\text{}_{C}Cstart
text, end text, start subscript, C, end subscript cells from
someone that has been exposed, and survived the same disease.
The T\text{}_{H}Hstart text, end text, start subscript, H, end
subscript cells act to activate other immune cells, while the
T\text{}_{C}Cstart text, end text, start subscript, C, end
subscript cells assist with the elimination of pathogens and
infected host cells.

Immunological memory
Because the adaptive immune system can learn and remember
specific pathogens, it can provide long-lasting defense and
protection against recurrent infections. When the adaptive
immune system is exposed to a new threat, the specifics of the
antigen are memorized so we are prevented from getting the
disease again. The concept of immune memory is due to the
body’s ability to make antibodies against different pathogens.
A good example of immunological memory is shown in
vaccinations. A vaccination against a virus can be made using
either active, but weakened or attenuated virus, or using specific
parts of the virus that are not active. Both attenuated whole
virus and virus particles cannot actually cause an active infection.
Instead, they mimic the presence of an active virus in order to
cause an immune response, even though there are no real
threats present. By getting a vaccination, you are exposing your
body to the antigen required to produce antibodies specific to
that virus, and acquire a memory of the virus, without
experiencing illness.
Some breakdowns in the immunological memory system can
lead to autoimmune diseases. Molecular mimicry of a self‐
antigen by an infectious pathogen, such as bacteria and viruses,
may trigger autoimmune disease due to a cross-reactive immune
response against the infection. One example of an organism that
uses molecular mimicry to hide from immunological defenses
is Streptococcus infection.

Innate Immunity vs. Adaptive Immunity: A

summary
The following chart compares and summarizes all of the
important parts of each immune system:

Attribute Innate Immunity Adaptive Immunity

Fast: minutes or
Response Time hours Slow: days

Highly specific! Can

Only specific for discriminate between
molecules and pathogen vs. non-
molecular patterns pathogen structures,
associated with and miniscule
general pathogens differences in
Specificity or foreign particles molecular structures

Macrophages,
Neutrophils, Natural
Killer Cells, Dendritic T cells, B cells, and
Major Cell Cells, Basophils, other antigen
Types Eosinophils presenting cells

Key Antimicrobial
Components peptides and Antibodies
 Attribute Innate Immunity Adaptive Immunity

proteins, such as
toxic granules

Not as good as the

innate immune
system, but still
pretty good at
determining which is
Innate immunity is which. Problems in
based on self vs. self vs. nonself
nonself discrimination result
Self vs. Nonself discrimination, so it in autoimmune
Discrimination has to be perfect diseases

Memory used can

lead to faster
response to recurrent
Immunological or subsequent
Memory None infections

Limited: Receptors Highly diverse: can be

used are standard customized by
and only recognize genetic
antigen patterns. No recombination to
new receptors are recognize epitopes
Diversity and made to adapt the and antigenic
Customization immune response determinants.
[Attribution and references]

Free learning resources

Use Khan Academy’s lea