5. Clonal Selection (def) and Clonal Expansion (def)
As mentioned above, during early differentiation of naive B-lymphocytes (def) in the bone marrow, each B-lymphocyte becomes genetically programmed to make an antibody with a unique antigen-binding site (Fab (def)) through a series of gene translocations, and molecules of that antibody are put on its surface to function as the B-cell receptor (see Fig. 1) . When an antigen encounters the immune system, its epitopes eventually will react only with B-lymphocytes with B-cell receptors on their surface that more or less fit and this activates those B-lymphocytes. This process is known as clonal selection (see Fig. 2).
Cytokines (def) produced by effector T4-helper lymphocytes (def) enable those activated B-lymphocytes to rapidly proliferate to produce large clones of thousands of identical B-lymphocytes. In this way, even though only a few B-lymphocytes in the body may have an antibody molecule able to fit a particular epitope, eventually many thousands of cells are produced with the right specificity. This is referred to as clonal expansion (see Fig. 3).
Furthermore, as the B-lymphocytes proliferate, they undergo affinity maturation (def) as a result of somatic hypermutations. This allows the B-lymphocytes to "fine-tune" the shape of the antibody for better fit with the original epitope. B-lymphocytes having better fitting B-cell receptor on their surface bind epitope longer and more tightly allowing these cells to selectively replicate. Eventually these variant B-lymphocytes differentiate into plasma cells (def) that synthesize and secrete vast quantities of antibodies that have Fab sites which fit the original epitope very precisely (see Fig. 4). It generally takes 4-5 days for a naive B- lymphocyte that has been activated to complete clonal expansion and differentiate into effector B-lymphocytes.
A single activated B-lymphocyte can, within seven days, give rise to approximately 4000 antibody-secreting cells. Over 2000 antibody molecules can be produced per plasma cell per second for typically up to four to five days. The B-memory cells (def) that eventually form also have these high affinity antibodies on their surface.
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by Gary E. Kaiser, Ph.D. Last updated: August, 2019 |
As with naive B-lymphocytes, during its development, each naive T4-lymphocyte becomes genetically programmed by gene-splicing reactions similar to those in B-lymphocytes, to produce a TCR (def) with a unique specificity. Identical molecules of that TCR are placed on its surface where they are able to bind an epitope/MHC-II complex (def) on an antigen-presenting dendritic cell with a corresponding shape (see Fig. 5). This is clonal selection of the T4-lymphocytes that are required for the body's response to T-dependent antigens (def).
In response to cytokines, these activated T4-lymphocytes now rapidly proliferate and differentiate into effector T4-lymphocytes (def). This is clonal expansion of the T4-lymphocytes.
Before an antigen enters the body, the number of naive T4-lymphocytes specific for any particular antigen is between 1 in 105 to 106 lymphocytes. After antigen exposure, the number of T4-lymphocytes specific for that antigen may increase to 1 in 100 to 1000 lymphocytes.