Clonal Selection and Expansion

CLONAL SELECTION AND EXPANSION

Within the body there may exist at any one time only a handful of naive B-lymphocytes capable of recognizing the same epitope. The meeting of an antigen and a naive B-lymphocyte capable of recognizing an epitope within the antigen occurs through the delivery of antigen to lymphoid tissues of the spleen, lymph nodes and local lymphoid tissue within mucosal surfaces (mucosal associated lymphoid tissue, MALT) and skin (SALT). This lymphoid tissue is rich in lymphocytes. Further, a proportion of B-lymphocytes will always be recirculating from the lymphoid tissue through the lymph and blood circulations and so able to encounter circulating antigen. Antigen will be specifically recognized by IgM molecules present on the surface of the naive B-lymphocyte. Following this antigen-driven selection of a specific B-lymphocyte clone, the clone will undergo repeated cell divisions. Some of the daughter cells will differentiate into short-lived (2–3 days) plasma cells able to secrete antibody of different classes to combat the initial primary antigen exposure. Other clonal daughter cells will become long-lived B-lymphocyte memory cells populating the lymphoid tissue and spreading around the body through the lymph and blood circulations. These cells will provide ‘immunological memory’ able to generate a more rapid and pronounced secondary response on subsequent exposure to the original antigen (Figure 9.5).

This process of clonal selection and expansion to form memory cell populations is the basis of vaccination. The initial introduction of antigen gives rise to a primary response (Figure 9.6) in which there is a significant latent period before increased serum antibody levels are observed; the main antibody response is IgM production, although some IgG is also synthesized and secreted. On re-exposure to the same antigen a secondary response is elicited. The features of the secondary response include:

•        a reduced latent period between antigen challenge and increases in serum antibody (e.g. latent period of 5–7 days for the secondary response vs 7–20 days for the primary response)

•        an antibody response dominated by IgG which is more pronounced with higher serum levels achieved.

In the absence of helper T-lymphocyte involvement (T-cell-independent humoral responses, e.g. where antigen is carbohydrate alone) B-lymphocyte memory cell populations are not produced, and antibody class switching is restricted. Hence, under these circumstances, the primary and secondary antibody responses to antigen challenge are essentially indistinguishable and exhibit a prolonged latent period, relatively low levels of serum antibody produced, and IgM as the main serum antibody.