Theories of Antibody production

Theories of Antibody production

1. Dr. P. Saranraj M.Sc., M.Phil., Ph.D., NET
Assistant Professor
Department of Microbiology
Sacred Heart College (Autonomous)
Tirupattur, Vellore District.
Mobile: [phone]
E.mail: [email protected]
THEORIES OF ANTIBODY
PRODUCTION

2. 1. SIDE CHAIN THEORY
The Side chain theory is a theory proposed by Paul
Ehrlich to explain the immune response in living cells.
Paul Ehrlich worked on Antitoxins for Diphtheria and
their binding to Antibodies in the blood. He hypothesized
that antibodies bind to antigens through special chemical
structures that he called "Side chains" (which he later named
"Receptors").
Paul Ehrlich Borrowed a concept used by Emil Fischer in
1894 to explain the interaction between an enzyme and its
substrate, Ehrlich proposed that binding of the receptor
to an infectious agent was like the fit between a “Lock
and Key”.

3. Paul Ehrlich published the first part of his Side chain theory
in 1897, and its full form in 1900 in a lecture he delivered
to the Royal Society in London.
According to the Side chain theory, Antibody producing
cells (B – cell) contains different side chains. When Antigen
encounters the Antibody producing cell, it can interact with
the side chains and select one of the side chains. It activates
Antibody producing cells and the activated cells then
produces Antibodies of selected side chain type.
Karl Landsteiner demonstrated that the Antibodies could
be formed not only against Antigens, but also against various
synthetic chemicals and the theory was abandoned.

4. 2. DIRECT TEMPLATE THEORY
Direct Template Theory was proposed by Breinl and
Haurowitz (1930), Alexander (1932) and Mudd
(1932).
According to this theory, Antigen enters into Antibody
forming cells (B – cell or Plasma cells) and act as a
“template” for the production of Antibody. Since, this
antibody is produced from antigen, it is specific for antigen.
The antibody specificity is predetermined before
encountering antigen because maturation of B - cell
occurs in antigen independent phase in bone
marrow. Because of this reason, Direct template theory
also disproved.

5. 3. INDIRECT TEMPLATE THEORY
Burnet and Fenner (1949) proposed this “Instructive
theory” to explain the synthesis of Antibody as an
Adaptive protein (biochemical functions of proteins by
repeated rounds of mutation and selection).
According to this Indirect template theory, antigen enters
into B - cell and it binds to its DNA and modifies it
and forms the modified DNA, antibodies are produced
against antigen and it also specific for it.
But in nature, there is no need for an antigen to enter
into B - cell and modify DNA for antibody
production because soluble antigen can activate B - cell by
binding to its cell surface receptor BCR. Because of this
reason, this theory also disproved.

6. 4. NATURAL SELECTION THEORY
Natural selection theory was proposed by Jerne in 1955.
According to Natural selection theory, serum will
contain antibodies for all antigens and these
antibodies are known as Natural antibodies.
Antibodies for blood group Antigen A and B can be given as
an example for this theory.
But, naturally serum will not contain secreted
antibodies for specific antigen till it enters host and
activates B - cell. Because of this valuable reason, this
theory also rejected.

7. 5. CLONAL SELECTION THEORY
Clonal selection theory is the present day theory which is
accepted universally.
Clonal selection theory was proposed by Frank
Macfarlane Burnet in 1957.
The Clonal selection theory explains the origin of
antibody formation.
According to the Clonal selection theory, each
immunologically competent B - cell possesses
receptor (for either IgM or IgD) that can combine
with one antigen. After binding of the antigen, the B -
cell is activated to proliferate and form a clone of cells.

8. In the process of Antibody production, Antigen selects a
single clone from multiple B - cell clone with
different specificity. Thus, this theory named as Clonal
selection theory.
After a clone is selected by antigen, B - cell is activated and
proliferated. After proliferation, selected B cells undergo
differentiation to form Plasma cell and Memory B –
cell for specific antigen.
Plasma cells secrete antibodies and they participate in
antigen removal.
The Clonal selection theory is also practically proved.