The Immune System 505The amino acid sequences of some antibodies have been
determined through the analysis of antibodies sampled from
people with multiple myelomas. These lymphocyte tumors
arise from the division of a single B lymphocyte, forming a
population of genetically identical cells (a clone) that secretes
identical antibodies. Clones and the antibodies they secrete are
different, however, from one patient to another. Analyses of
these antibodies have shown that the F (^) c regions of different
antibodies are the same (are constant), whereas the F (^) ab regions
are variable. Variability of the antigen-binding regions is
required for the specificity of antibodies for antigens. Thus, it
is the F (^) ab region of an antibody that provides a specific site for
bonding with a particular antigen to form an antigen-antibody
complex ( fig. 15.9 ).
B lymphocytes have antibodies on their plasma mem-
branes that serve as receptors for antigens. Combination
of antigens with these antibody receptors stimulates the B
cell to divide and produce more of these antibodies, which
are secreted. Exposure to a given antigen thus results in
increased amounts of the specific type of antibody that
can attack that antigen. This provides active immunity, as
described in section 15.4.
Diversity of Antibodies
It is estimated that there are about 100 million trillion (10^20 )
antibody molecules in each individual, representing a few
million different specificities for different antigens. Because
antibodies that bind to particular antigens can cross-react with
closely related antigens to some extent, this tremendous anti-
body diversity usually ensures that there will be some anti-
bodies that can combine with almost any antigen a person
might encounter. These observations evoke a question that
has long fascinated scientists: How can a few million differ-
ent antibodies be produced? A person cannot possibly inherit
a correspondingly large number of genes devoted to antibody
production.
Two mechanisms have been proposed to explain antibody
diversity: (1) antigen-independent genetic recombination in
the bone marrow; and (2) antigen-dependent cell division of
lymphocytes in the secondary lymphoid organs.
The antigen-independent generation of antibody diver-
sity is due to different combinations of heavy and light chains,
which produce antibodies with different specificities. As a
result, a person does not have to inherit a million different
genes to code for a million different antibodies. If a few hun-
dred genes code for different H chains and a few hundred code
for different L chains, different combinations of these poly-
peptide chains could produce millions of different antibodies.
The number of possible combinations is made even greater
by the fact that different segments of DNA code for differ-
ent segments of the heavy and light chains. Three segments
in the antigen-combining region of a heavy chain and two in
a light chain are coded by different segments of DNA and can
be combined in different ways to make an antibody molecule.
Recombination of these genes in the developing lymphocytes
of the bone marrow is antigen-independent and is responsible
for the initial large diversity of B cells with different antibody
receptors for different antigens.
The antigen-dependent generation of antibody diver-
sity occurs as B cells proliferate in the secondary lymphoid
organs (such as the spleen and lymph nodes) in response to
antigens. This diversification occurs by hypermutation (a
high rate of mutations) of single base pairs in DNA. Because
mutations in body cells, rather than germ cells (sperm or
ova), are called somatic mutations, this mechanism is called
somatic hypermutation. Antigen-dependent diversification
of antibodies also occurs by gene recombinations. There is a
switch in the constant regions of the heavy chains of the anti-
bodies, so that the original IgM antibodies are converted into
IgG, IgA, or IgE antibodies (see fig. 15.8 and table 15.6 ).
This is called class switch recombination.
Figure 15.9 The formation of an antigen-antibody
complex. There are two antigen binding sites, composed of
portions of the heavy and light chains, per antibody molecule.
These bond to two specific antigens to form an antigen-antibody
complex.
Light chain
of antibody
Antigen
Heavy chain
of antibody
Antigen-Antibody
Complex
(a)
(b)