Theories of Antibody Production

Theories of antibody production

Instructive theory 

Haurowitz and Breinl in 1930, proposed this theory.  According to the instructive theory; antibodies are a distinct class of proteins but have no fixed structures. The specificity is determined by the antigen. Single antigen-producing cells can generate multiple specificities of antibodies.

It says that antigen functions as a template around which antibody is formed and after being formed it is stabilized by interchain binding and is released in the blood. In this theory, since antigen (Ag) guides the production of antibody so it is known as "Instructive theory. Of antibody production".

Two instructive theories are postulated as follows:

Direct Template Theory

This theory states that the first step in antibody production is the entry of antigen into the antibody-producing cell. The antibody-producing cell uses this antigen as a mold to modify the structure of the antibody. As a result, the cell produces globulin molecules that are specific to the antigen. The antigen-specific structured antibody is released into the blood and the antigen cast is reused.

Indirect Template theory

Burnt and Fenner in 1949 postulated the indirect template theory. This theory suggests that the genome of the antigenic determinants gets incorporated into the genome of the antibody-producing cells, inducing heritable change in them. These altered cells then generate antigen-specific antibodies against the antigen.

Immune network theory

Carl Jerne in 1974 proposed the immune network theory. This theory explains the working behavior and mechanism of the immune system. It explains how the adaptive immune system works. Niels K Jerne proposed that the antibodies of the system not only identify foreign antigens but also recognize and interact with each other, as part of a network. The theory narrates that the immune system is an interconnected network of lymphocytes and molecules that have variable (V) regions. These V regions attach not only to things that are foreign to the host body but also to other V regions within the system. The immune system is therefore recognized as a network, with the parts associated with each other by V-V interactions.

Selective Theories of Antibody Poduction

Selective theories suggest that it is not antigen, but the antibody molecule that plays a central role in determining its specificity. The immune system already possesses pre-formed antibodies of different specificities before encountering an antigen. Three selective theories were postulated as follows:

Side chain theory

Paul Ehrlich gave the first theory of antibody production in 1900. He hypothesized the lock and key fit model of antigen-antibody combination.

According to Ehrlich’s side chain theory; the specificity of the globulin side that is a receptor, is fixed, and the antigen binds to the suitable pre-structured receptor. This model also allows a particular cell to generate antibodies of multiple specificities.

This theory states that the outer surface of certain cells in the body has side chains that can combine with the foreign proteins and toxins by complementary-shaped fit which later gets released from the surface of the cells. As a result of the loss of receptors, the cell produced more receptors at a higher speed. These excess receptors are detached from the cell and circulate throughout the body. Ehrlich believed these receptors as “antibodies”. he first described antibodies as “magic bullets”.

Natural selection theory

Jerne put forward the model of Natural Selection for antibody formation in 1955. According to this theory, all possible globulin molecules, each with pre-determined specificity for the entire range of antigens, are produced in the serum in minute amounts during embryonic life.

This theory states that after entering the body, the foreign antigen that binds with particular globulin molecules having specific receptors is taken up by phagocytic cells. The phagocytic cells then synthesize replicas of the globulin molecule receptors, which are released as antibodies.

Clonal selection theory

Clonal selection theory was proposed by Burnet in 1957. This theory is regarded as a keystone in modern immunology because it has become the most widely accepted model for how our immune system behaves against infections and how several B cells and T cells are determined to destroy particular antigens entered into the body. 

According to this theory; the antibodies containing B cells are synthesized by stem cells of bone marrow found in our bones. These B cells are precursor B cells that proliferate and undergo several changes in their genes due to which cells with different receptors are synthesized, each having a specific antibody receptor for a specific antigen. These B cells are released in the lymphoid organs such as blood or lymph nodes.

 When an antigen enters the blood, it binds to its specific antibody receptor on B cells. The antigen-specific B cells get activated and start to divide to make two types of clones i.e. the plasma cells which will release antibodies to eliminate the invaded antigen and the memory B cells which keep a record of the antigen entering the body. When the same antigen enters the body, the memory B cells immediately recognize and destroy the antigen. 

This theory states that the antibodies are already made in the body but they are released at the time of exposure to antigens. Clonal selection theory also provides a system for immunological tolerance that gives us information about antibody-producing cells which eliminate or destroy any specific antigen encountered during fetal life.