B cell activation: 

Introduction:

B cell activation is the process that precedes the transformation of B cells to plasma cells and
memory B cells. The plasma cells in turn produce antibodies. The antibodies serve a critical role
in an immune response against foreign attackers in your body.

Importance of Antibodies as products of B Cell Activation

Antibodies are proteins produced by the B cells in response to antigen challenges. The antibodies
mediate humoral immunity which is one arm of the adaptive immune system. Once, produced
antibodies coordinate several effector mechanisms in your body to eliminate the attacking
antigen.

Mechanism:

Neutralization of the antigens

The antibodies in this case specifically bind to all the epitopes (active sites) of the antigens
making the continued multiplication of the antigen/microorganisms come to a halt. This
effectively helps the other cells of the immune system that have receptors for those antibodies to

clear the infection.

Activation of Complement

Through the classical pathway of the complement system, antibodies combine with antigens to
make complexes and initiate the complement activation process on the cell walls of
microorganisms. The ultimate outcome of this process is the formation of the membrane attack
complex (MAC) which helps in making pores on the walls of bacteria which kills them.
Antibody-Dependent Cellular Cytotoxicity (ADCC)

Some cells like the cytotoxic T lymphocytes and the natural killer cells are guided by antibodies
which specifically tag the attacking antigens. These cells have receptors for the Fc regions of the
antibodies and bind them. This binding causes these cells to release their Cytotoxicity granules
(Granzymes and perforins) that help kill the microorganism.

B cell Activation Process:

The process of B cell activation occurs in the secondary lymphoid organs. The secondary
lymphoid organs involved here include the spleen and various lymph nodes around your body.
Firstly, the B cells develop in the bone marrow through seven B cell development stages to
become mature B cells, the last stage of their development.  

The mature B cells are now available in your blood circulation ready to encounter antigens. The
B cells recognize antigens through their B cell receptors (BCRs). For this to happen there must
be specificity between the epitopes (Ab-binding active parts) of the antigens and the BCR
(membrane-bound immunoglobulin).

This activation eventually gives rise to plasma cells as well as memory B cells. The activation of
B cells is important in your body.  During an attack, it is only through this process that your
immune system can make antibodies.  Antibodies are the cornerstones of the humoral immune
response that eliminates the attacker through several effector mechanisms. 

Step-By-Step B cell Activation

The mature B cells are always available in your blood circulation. They can access different
secondary lymphoid organs through the blood vessels. On the other hand, the attacking antigens
are also taken to the secondary lymphoid organs (Spleen, lymph nodes) through the lymphatic
system.
In the spleen and/or lymph nodes, the B cells through BCRs interact with the antigens. The B
cells will scan antigens and the B cells with BCR specific to the antigens will bind. This binding
will act as a switch or key to a complex signaling process that will lead to the multiplication of
that clone of B cells to several copies (clonal expansion).

Germinal Centers’ Activities:

Germinal centers (GCs) are structures that are formed during an immune response in the B cell
zones or follicles. This occurs within the spleen or lymph nodes. We have two paths through
which the B cells can be activated here. This can be through the T-Independent path or through
the T-dependent path of the immune response.

B cell activation sometimes occurs through T-help cells

In the T-independent path immune response, the BCR interacts directly with the specific epitopes
of the attacking antigen. On the other hand, in the T-dependent path, the T helper cells must be
available to help the B cells. Therefore, where the T helper cells’ assistance is needed the B cells
move closer to the T cell zones border.

The T cell through CD40L on its surface interacts with CD40 coreceptor on the surface of the B
cell. There is also going to be upregulation of the cytokine receptors on the B cell surface. The
cytokines whose receptors will be expressed here include IL-21, IL-4 and IL-10.
The T cells (TH2) produce important cytokines (IL-21, IL-4 and IL-10) that help fasten the
process of B cell activation and proliferation in the germinal centers. It is important to note that
in the active state, the mature B cells have IgM/IgD serving as BCR.

However, after activation, the B cells can change (Hyper mutate) to IgG, IgA, or IgE The B cells
may also retain IgM on their surface while some IgM may be available as free serum
immunoglobulin. This act of changing one immunoglobulin isotype to the other is known as
class switching.  

End-Product of B cell Activation – Plasma Cells and Memory B cells

Whichever path they use the B cells once activated will end up being either plasma cells or
memory B cells. Plasma cells are short-lived cells that produces antibodies specific to the
original antigen that was recognized by the mature cells’ BCRs.

The plasma cells will exit the germinal centers and migrate to the bone marrow where they help
clear antigens therein. The memory B cells on the other hand will exit to go into the blood
circulation where they can live for many years. They confer long-lived protection.

Whenever the same antigen they are specific for comes around, it will quickly be dealt with
before sickness sets in your body. Therefore, the long-term protection induced by vaccines in the
process of immunization is partly provided by the memory B cells. The other part is about
memory T lymphocytes. 

In a nutshell, the B cells are activated through the following stages as indicated in the diagram in
this section. The activation process begins with mature B cells interacting with antigens, then
formation of lymphoblast, then GC B cells, and finally, differentiates to either plasma B cells or
memory B cells.
 The flow diagram of the B cell activation process (istock)

Both plasma B cells and memory B cells possess high-affinity BCR for their specific antigen.
Review the diagram above for conceptualization of how this process happens.  Note that plasma
cells are the only cells in the diagram that produce antibodies. They are also the only cells in
your immune system that produce antibodies.