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Instructional theory vs Selective theory

Instructional theories postulated that antigens play a central role in determining antibody specificity. Conversely, selective theories stated that an antigen reacts with an already-existing antibody.

Below is a history of antigen-antibody theories. Selective theories better explained acquired immune responses. Nowadays, the Clonal Expansion Theory is the accepted explanation of antibodies and their origin.

Paul Ehrlich
(c 1900)
According to Ehrlich's Side Chain Theory, an antigen binds to a side chain receptor (Nutrient R, ingested via eating) and results in release of the side chain. This induces the cell to produce and release more side chains of the same specificity. This is a selective theory because the side-chain (antibody) repertoire exists independently of exposure to antigen -- the antigen simply binds to particular side chains and stimulates their production.
Karl Landsteiner
(c 1935)
Landsteiner modified antigens into structures that had never existed before, and found they all induced antibody production. Researchers wondered why people would have antibodies for non-existent antigens, and how this specificity could occur with a limited number of genes. Thus, selective theories lost favor.
Linus Pauling
Linus Pauling spearheaded instructional theories, which proposed that antigens encountered antibody templates. These antibody templates would wrap around the antigen, forming a complementary molecular which would neutralize similar antigen molecules in the future. While these theories explained specificity and diversity, they did not explain: how the body recognized self from non-self, as a blank template would be blind; memory, since subsequent responses to a particular antigen are exponentially higher and faster than in the initial encounter.
(c 1950)

Burnett's Clonal Selection Theory assumes that there are certain cells dedicated to making antibody, and that this is where antibody diversity is generated, stored and expressed. In simple terms:

  1. Every cell in this population makes a single kind of antibody with its own unique antigen specificity.
  2. The antibody the cell makes is determined randomly, completely independent of the antigenic universe.
  3. The cell displays a copy of the antibody it makes on its cell surface.
  4. Any cell making antibody reactive with self is eliminated or silenced.
B cells were discovered approximately fifteen years after Burnett's Clonal Selection Theory, proving that antibodies all pre-exist and that the repertoire is independent of the antigenic universe.

This validated Burnett's theory as well as Ehrlich's similar (although much older) proposal. However, two key facets of Ehrlich's theory were also disproven: B cells are exclusively dedicated to antibody production; and antibodies are not from food. The Clonal Expansion Theory is the modern explanation for antibodies and their origin.

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