Theories of antibody formation
There are two sets of theories of antibody formation. These are instructive theory and selective theories.
Instructive theory suggests that an immunocompetent cell is capable of synthesizing antibodies of all specificity. The antigen directs the immunocompetent cell to produce complementary antibodies. Two instructive theories are postulated as follows:
Direct template theory: This theory was first postulated byBreinl and Haurowitz (1930). They suggested that a particu-lar antigen or antigenic determinants would serve as a template against which antibodies would fold. The antibody molecule would thereby assume a configuration complementary to antigen template.
Indirect template theory: This theory was first postulated byBurnet and Fenner (1949). They suggested that the entry of anti-genic determinants into the antibody-producing cells induced a heritable change in these cells. A genocopy of the antigenic determinant was incorporated in genome and transmitted to the progeny cells. However, this theory that tried to explain specificity and secondary responses is no longer accepted.
Three selective theories were postulated as follows:
Side chain theory: This theory was proposed by Ehrlich (1898).According to this theory, immunocompetent cells have surface receptors that are capable of reacting with antigens, which have complementary side chains. When antigens are introduced into host, they combine with those cell receptors that have a complementary fit. This inactivates the receptors. There is an overproduction of the same type of receptors that circulate as antibodies, as a compensatory mechanism.
Natural selection theory: This theory was proposed by Jerne(1955). According to this theory, during the embryonic life, mil-lions of globulin molecules were formed against all possible range of antigens. The antigen when introduced to the host combines selectively with the globulin molecule that has the nearest comple-mentary fit. The globulin with the combined antigen stimulates antibody-forming cells to produce the same type of antibody.
Clonal selection theory: Burnet (1957) suggested that immu-nological specificity existed in the cell but not in the serum and proposed the most acceptable clonal selection theory. According to this theory, a large number of clones of immunological com-petent cells bearing specific antibody patterns are produced during fetal development by a process of somatic mutations of immunological competent cells (ICCs) against all possible antigens.
This theory suggests that an individual ICC expresses mem-brane receptors that are specific for a distinct antigen. This unique receptor specificity is determined before the lympho-cyte is exposed to antigen. Binding of antigen to its specific receptor activates the cell and leads to cellular proliferation to form clones, synthesizing the antibody.
The clonal selection theory is most widely accepted and pro-vides a framework for better understanding of the specificity, immunological memory, and the property of recognition of self and nonself by adoptive immunity.