The Biology Project: Immunology

Immunology Problem Set

Problem 9: Clonal selection theory

Tutorial to help you answer the question:

The clonal selection theory of antibody diversity says:

A. B cell precursors randomly rearrange variable coding parts of antibody genes. Afterwards, antigen binds to a clone with specific membrane antibody, resulting in differentiation to antibody secreting plasma cells
B. The antigen causes a nonspecific clone of B lymphocytes to proliferate and secrete antibody molecules capable of binding to any foreign antigen
C. Antigen causes the growth of a clone of lymphocytes which then rearrange DNA, creating a gene coding for a specific antibody
D. A clone of macrophages with specific receptor for antigen phagocytoses antigen, then rearranges DNA to generate specific antibody-coding genes


Clonal selection and immunological memory

Clonal selection theory illustrates how immunological memory permits a rapid response upon a second exposure to an antigen. Immunological memory is the basis of natural immunity and artificial immunity (from vaccinations).

Each B cell has a specific antibody as a cell surface receptor. The arrangement and generation of antibody genes occurs prior to any exposure to antigen. When a soluble antigen is present, it binds to the antibody on the surface of B cells that have the correct specificity. These B cell clones develop into antibody-producing plasma cells or memory cells. Only B cells, which are antigen-specific, are capable of secreting antibodies.

Following initial exposure to antigen, the plasma cells stop producing antibody and die. Memory cells remain in greater numbers than the initial B cells, allowing the body to quickly respond to a second exposure of that antigen.

The body can make low levels of soluble antibody about one week after exposure to antigen. However, a second exposure to antigen produces a much faster response, and several orders of magnitude higher levels of antibody. The ability of antibody to bind antigen also increases in the secondary response. The memory of antigen and stimulated response is the basis for vaccination.

A secondary immune response (second exposure to an antigen) is not only faster but produces antibody with up to a 10,000 fold increase in binding affinity. This higher affinity comes from a mechanism that alters the variable regions of light and heavy chains of the memory cells by specific somatic mutation. This is a random process that by chance can improve antigen binding.
The system makes a mutation for each two cell divisions. Re-exposure to antigen is most likely to cause clonal expansion of memory cells which produce the highest affinity antibody. The mutations which lead to increased affinity will be clonally selected by antigen similarly to the primary response. Cells with inactive antibody will die by apoptosis from a lack of T cell signaling.


Problem 9 | Answer | Problem 10

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