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Clonal Selection

Clonal Selection
Antigen selects those lymphocytes that possess the specific receptor
Each B‐cell is programmed to make one, and only one, specificity of antibody and it places a transmembrane version of these antibodies on its cell surface to act as receptors for the specific antigen. These antibodies can be detected by using fluorescent probes and, in Figure 2.8c, one can see the molecules of antibody on the surface of a human B‐lymphocyte stained with a fluorescent rabbit antiserum raised against a preparation of human antibodies. Each B‐lymphocyte has of the order of 105 antibody molecules, all of identical antigen specificity, on its surface. The B‐cells give rise to plasma cells (Figure 2.8 d,e), which produce large amounts of soluble antibody in their rough endoplasmic reticulum (Figure 2.8 f ). The antibody is then secreted from the plasma cells into the local environment and can circulate, become attached to cells bearing Fc receptors, or be transported to mucosal surfaces.
Cells involved in the acquired immune response. (a) Small lymphocyte. Typical resting lymphocyte with a thin rim of cytoplasm. Condensed chromatin gives rise to heavy staining of the nucleus. Giemsa stain. (Source: A.V. Hoffbrand, J.E. Pettit, and P.A.H. Moss (2006) Essential Haematology, 5th edn. Reproduced with permission of Wiley.) (b) Electron micrograph of a lymphocyte with an indented nucleus containing condensed chromatin, sparse cytoplasm: single mitochondrion shown

When an antigen enters the body, it is confronted by a dazzling array of B‐lymphocytes all bearing different antibodies each with its own individual recognition site. The antigen will only bind to those receptors with which it makes a good fit. B‐lymphocytes whose receptors have bound antigen receive a triggering signal and can then develop into either plasma cells or memory B‐cells. As the B‐lymphocytes are programmed to make only one specificity of antibody, the soluble version of the antibody molecule secreted by the plasma cell will recognize the same antigen as the cell surface transmembrane version originally acting as the antigen receptor. In this way, antigen selects for the production of the antibodies that recognize it effectively (Figure 2.11a). T‐cells with a TCR of appropriate specificity are similarly selected (Figure 2.11b), which can include the T‐helper cells that are required in most cases to help B‐cells proliferate and subsequently differentiate into plasma cells.

The need for clonal expansion means humoral immunity must be acquired
Because we can make hundreds of thousands, maybe even millions, of different antibody molecules, it is not feasible for us to have too many lymphocytes producing each type of antibody; there just would not be enough room in the body to accommodate them. To compensate for this, lymphocytes that are triggered by contact with antigen undergo successive waves of proliferation to build up a large clone of plasma cells that will be making antibody of the kind for which the parent lymphocyte was programmed. By this system of clonal selection, large enough concentrations of specific antibody can be produced to combat infection effectively (Milestone 2.1; Figure 2.11a). Clonal selection of T‐lymphocytes similarly ensures that only cells of the appropriate specificity are induced to proliferate.
The importance of proliferation for the development of a significant antibody response is highlighted by the ability of antimitotic drugs, which prevent cell division, to completely abolish antibody production to a given antigen stimulus.
Because it takes time for the proliferating clone to build up its numbers sufficiently, it is usually several days before antibodies are detectable in the serum following primary contact with antigen. The newly formed antibodies, and newly expanded T‐cells, are a consequence of antigen exposure and it is for this reason that we speak of the acquired (adaptive) immune response.