The major players of humoral immunity are
B-cells.
They develop in the bone marrow and complete
their maturation in the spleen.
Similar to T-cells, B-cells are formed in
billions of variations, each carrying a unique
surface protein, called B-cell receptor, BCR.
Just like T-cells, they also learn to not
react to the body’s own antigens; those
that react to self-molecules are eliminated
or ignored.
The majority of mature B-cells, namely the
follicular B-cells, circulate to secondary
lymphoid organs - the same locations as mature
T-cells, where they expect encounters with
pathogens.
T-cells and B-cells are usually separated
into defined T-cell and B-cell zones within
these organs.
Here again, specific immunity relies on the
invading pathogen finding a match among these
many variations of B-cells.
Only cells that can bind to the pathogen,
can be activated to produce antibodies.
B-cell surface receptors, BCRs, are actually
membrane-bound antibodies.
The existence of BCR variations means that
the body already has all the antibodies it
can possible make right from the start.
For resource management purposes, it makes
sense not to produce all of them in large
quantities.
Instead, presence of an invading pathogen
selectively activates the binding B-cell,
which then multiplies and produces huge amounts
of that particular antibody to combat the
pathogen.
An antibody is basically a protein whose structure
consists of variable and constant regions.
The variable regions give the antibody its
uniqueness, much like the bit, or blade, of
a key.
This is where it binds to a specific antigen,
which is the lock.
There are several classes of antibodies, differing
in their constant regions.
Different antibody classes engage different
mechanisms to neutralize the antigen.
The surface receptors on B-cells are IgM and
IgD molecules.
Each B-cell has thousands of identical copies
of BCR on its surface.
When a pathogen binds, it usually binds to
several of these receptors, linking them together,
triggering endocytosis of the pathogen.
B-cells then cut the pathogen into pieces
and display them on MHC-II molecules on their
surface.
Thus, B-cells now become antigen-presenting
cells, but are not yet activated.
In most cases, activation of antigen-primed
B-cells does not happen until they are stimulated
by antigen-specific T-helper cells.
Nearby, in the T-cell zone, T-helper cells
are activated by dendritic cells carrying
antigens of the same pathogen, and become
effector T-helper cells.
Some of these effector cells leave lymph nodes
for the site of infection, while other, namely
the follicular helper cells, migrate to T-cell
B-cell borders, and bind to the antigens presented
by B-cells.
This interaction triggers T-cells to produce
helper factors, which activate B-cells.
Activated B-cells undergo first rounds of
proliferation and differentiation, giving
rise to the first batch of plasma cells producing
antibodies, mainly of IgM class; and a group
of cells that are committed to become memory
B-cells.
The latter undergo antibody class switching;
and form a so-called germinal center, where
they go through cycles of multiplication and
hypermutation in the immunoglobulin gene.
This process produces slightly different variations
of the same antibody, which are then subject
to a binding test to the same antigen.
Those that no longer bind are discarded, while
the remaining compete for binding to antigen-specific
T-helper cells.
B-cells with the highest affinity to the antigen
win the interaction with T-helpers and exit
the germinal center.
They can either become long-lived memory B-cells,
or differentiate into antibody-producing plasma
cells.
This second batch of plasma cells produces
better antibodies and lives longer than the
first batch.
They also make antibodies of different classes
(predominantly IgG), which neutralize the
pathogen in many different ways.
Upon reexposure to the same pathogen, memory
B-cells mount a much faster immune response.
Plasma cells form within hours, producing
huge amounts of the best possible antibody
within days, destroying the pathogen so quickly
that no signs of illness are noticeable.
