Clonal selection is a theory that attempts to explain why lymphocytes are able to respond to so many different types of antigens. T and B cells are able to respond to nearly all of the world’s wide variety of antigens upon presentation. Clonal selection assumes that lymphocytes are selected during antigen presentation because they already have receptors for that antigen.

In clonal selection, an antigen is presented to many circulating naive B cells and (via MHC) T cells, and the lymphocytes that match the antigen are selected to form both memory and effector clones of themselves. This mass production is termed “clonal expansion,” in which daughter cells proliferate into several generations of clones of the original parent cells. The theoretical basis of clonal selection is the assumption that lymphocytes bearing an antigen receptor for an antigen exist long before antigen presentation occurs, explained by the idea of random mutations (VDJ recombination) that occur during lymphocyte maturation. During antigen presentation, pre-existing lymphocytes that bear that antigen receptor are merely selected because they can bind with that antigen. It is also assumed that most lymphocytes never encounter the antigen for which they bear a receptor.

Clonal selection may also be used during negative selection during T cell maturation. Here, the body’s epitopes are presented to the infant lymphocytes; those that react are recognized as auto-reactive and destroyed before they (and their future cloned daughter cells) can leave and wreak havoc in the body. This assumes that random mutations resulted in lymphocytes that were autoreactive instead of reactive to non-self antigens.

Following an adaptive immune response, memory cells can respond to a new infection of the same pathogen much more quickly than the original effector T cells during the formation of the adaptive immune response. Clonal selection is thought to cause mutations of antigen-binding affinity in memory cells during clonal expansion so that memory cells have greatly increased antigen-binding affinity than the effector cells during the first response. The increased binding affinity may be why memory cells can eliminate a pathogen more rapidly than the original generation of effector cells.

Key Points

• Clonal selection is used during negative selection to destroy lymphocytes that may be able to bind with self-antigens.

• Clonal selection is the theory that specific antigen receptors exist on lymphocytes before they are presented with an antigen due to random mutations during initial maturation and proliferation. After antigen presentation, selected lymphocytes undergo clonal expansion because they have the needed antigen receptor.

• Clonal selection may explain why memory cells can initiate secondary immune responses more quickly than the primary immune response, due to increased binding affinity from clonal expansion.

Key Terms

clonal selection: The idea that lymphocytes have antigen-specific binding receptors before they encounter with an antigen, and are selected to proliferate because they have the specific antigen receptor needed during an adaptive immune response.

antigen: A substance that induces an immune response, usually a molecule found on a pathogen such as a toxin or molecule expressed by the pathogen or pathogen-infected cells.

T cell: a lymphocyte, from the thymus, that can recognize specific antigens and can activate or deactivate other immune cells

B cell: a lymphocyte, developed in the bursa of birds and the bone marrow of other animals, that produces antibodies and is responsible for the immune system

lymphocytes: white blood cells involved in adaptive immunity

clonal expansion: production of daughter cells all arising originally from a single cell. In a clonal expansion of lymphocytes, all progeny share the same antigen specificity

VDJ recombination: the process by which T cells and B cells randomly assemble different gene segments

epitope: the part of an antigen molecule to which an antibody attaches itself

adaptive immunity: a specific type of immunity developed over time

pathogen: any organism or substance, especially a microorganism, capable of causing diseases, such as bacteria, viruses, protozoa, or fungi

memory cells: a long-lived lymphocyte capable of responding to a particular antigen on its reintroduction, long after the exposure that prompted its production.