Clonal Selection
Antigen selects those lymphocytes that possess the
specific receptor
Each B‐cell is
programmed to make one, and only one, specificity of antibody and it places a
transmembrane version of these antibodies on its cell surface to act as
receptors for the specific antigen. These antibodies can be detected by using
fluorescent probes and, in Figure 2.8c, one can see the molecules of antibody
on the surface of a human B‐lymphocyte stained with a fluorescent rabbit
antiserum raised against a preparation of human antibodies. Each B‐lymphocyte
has of the order of 105 antibody molecules, all of identical antigen
specificity, on its surface. The B‐cells give rise to plasma cells (Figure
2.8 d,e), which produce large amounts of soluble antibody in their rough
endoplasmic reticulum (Figure 2.8 f ). The antibody is then secreted from the
plasma cells into the local environment and can circulate, become attached to
cells bearing Fc receptors, or be transported to mucosal surfaces.
When an antigen enters
the body, it is confronted by a dazzling array of B‐lymphocytes all bearing
different antibodies each with its own individual recognition site. The antigen
will only bind to those receptors with which it makes a good fit. B‐lymphocytes
whose receptors have bound antigen receive a triggering signal and can then
develop into either plasma cells or memory B‐cells. As the B‐lymphocytes are
programmed to make only one specificity of antibody, the soluble version of the
antibody molecule secreted by the plasma cell will recognize the same antigen
as the cell surface transmembrane version originally acting as the antigen
receptor. In this way, antigen selects for the production of the antibodies
that recognize it effectively (Figure 2.11a). T‐cells with a TCR of appropriate
specificity are similarly selected (Figure 2.11b), which can include the
T‐helper cells that are required in most cases to help B‐cells proliferate and
subsequently differentiate into plasma cells.
The need for clonal expansion means humoral immunity
must be acquired
Because we can make
hundreds of thousands, maybe even millions, of different antibody molecules, it
is not feasible for us to have too many lymphocytes producing each type of antibody; there just would not be
enough room in the body to accommodate them. To compensate for this,
lymphocytes that are triggered by contact with antigen undergo successive waves
of proliferation to build up a large clone of plasma cells that will be making
antibody of the kind for which the parent lymphocyte was programmed. By this
system of clonal selection, large enough concentrations of
specific antibody can be produced to combat infection effectively (Milestone
2.1; Figure 2.11a). Clonal selection of T‐lymphocytes similarly ensures that only
cells of the appropriate specificity are induced to proliferate.
The importance of
proliferation for the development of a significant antibody response is
highlighted by the ability of antimitotic drugs, which prevent cell division,
to completely abolish antibody production to a given antigen stimulus.
Because it takes time
for the proliferating clone to build up its numbers sufficiently, it is usually
several days before antibodies are detectable in the serum following primary
contact with antigen. The newly formed antibodies, and newly expanded T‐cells,
are a consequence of antigen exposure and it is for this reason that we speak
of the acquired (adaptive) immune response.
