Clonal Selection Theory

Antibody Diversity - The clonal selection theory explains how the body has an inherent ability to produce an immense diversity of antibodies with different amino acid sequences that are able to bind an enormous range of antigens. The basic postulates, illustrated in Figure 7.30, are the following:

> 1. B stem cells in the bone marrow differentiate to become B lymphocytes, each producing a slightly different type of immunoglobulin molecule, each type with a binding site that will recognize specific molecular shapes. These immunoglobulins, or antibodies, are attached to the cell membrane and exposed on the outer surfaces of the B lymphocytes.

> 2. Binding of an antigen to one of these antibodies stimulates the cell carrying it to replicate, generating a clone (a collection of cells with identical genetic information). This primary response is aided by a special class of T cells called helper T cells. If a helper T cell recognizes a bound antigen, it binds to the appropriate B lymphocyte and transmits to it a signal protein (interleukin-2) that stimulates B-cell reproduction. Thus, those clones of B cells that recognize antigens are stimulated to continued cell division.

> 3. Two classes of cloned B cells are produced (Figure 7.30 and Figure 7.31). Effector B cells, or plasma cells, produce soluble antibodies, which are excreted into the circulatory system. These antibodies have the same antigen binding sites as the surface antibodies of the B lymphocyte from which the effector cells arose, but they lack the hydrophobic tail that bound the surface antibodies to the lymphocyte membrane. The other class of cells in the clone-memory cells - will persist for some time, even after antigen is no longer present. This persistence constitutes the immune memory. That is it allows a rapid secondary response to a second stimulation by the same antigen, as shown in Figure 7.31.

Lack of Immunity to Self - We do not find clones producing antibodies against our own proteins and tissues because when immature B cells in the fetus encounter substances that bind to their surface antibodies, they are not stimulated to replicate. Rather, these cells are destroyed. Thus, cells producing antibodies against all of the potential "self" antigens to which we might react are eliminated before birth. The only B cells that mature are those that produce antibodies against "nonself" substances.

Autoimmunity - Occasionally, the immune system goes awry and produces antibodies against the normal tissues of an adult. The reasons for such autoimmunity are not wholly understood, but the resulting diseases can be devastating. In lupus erythematosus, for example, the individual's own nucleic acids become the object of attack.

See also: The Immune Response, Antibody Structure, Generation of Antibody Diversity, T Cells and the Cellular Response, Interleukin-2