| Themes > Science > Life Sciences > General Biology > Immunology > Recognition Systems in Immunity > Antigen Recognition: B Cells and Antibodies > Class switching and affinity maturation |
The mature B cell can produce both mu and delta chains expressing the same V region. Ig genes are first expressed as long RNA transcripts containing the VDJ as well as sequences for both Cmu and Cdelta. Alternative RNA splicing will generate either chain. The switch from membrane bound Ig to secreted Ig is regulated by RNA cleavage depending on the choice of polyadenylation sites; each B cell can make both membrane bound and secreted forms. Rearranged VDJ genes can recombine to different C regions by switch recombination and deletion of intervening DNA. The switch regions are conserved pieces of DNA found at the 5' end of each CH locus. We will discuss the role that T lymphocytes play in controlling isotype switching later. |
| Affinity maturation is a
consequence of somatic mutation in Ig gene segments. There is a special
mechanism for inducing mutations in rearranged V regions (VDJ). Cells
expressing mutations which improve antigen binding are favoured in terms
of activation and co-operation with T cells. Thus during an immune
response particularly as the free concentration of antigen falls the
average affinity of antibodies produced increases as higher affinity
clones are selected. The corollary of this phenomenon is that many B cell
clones are discarded since most mutations are deleterious. The rate of
mutation is 1 per 1000 for each V gene base pair per cell division
compared to 1 per 1000000 for each base pair per cell division for normal
DNA
Protein antigens do not induce antibody responses in the absence of T lymphocytes, they are T dependent. Non-protein antigens, polysaccharides and lipids for example, can give antibody responses without T cells (T independent). T independent antigens are usually polymeric and it is believed that they cross link membrane Ig on B cells sufficiently well to activate them without co-operation from T cells. The antibodies to these antigen are invariably IgM and do not demonstrate affinity maturation. We will discuss the co- operation between T and B cells in a later lecture. Affinity and avidityThese terms are often used in a confusing way, even in textbooks. A clearer expression is monovalent affinity since the affinity of an antibody (or other receptor) is really the strength of interaction between one antibody combining site and one corresponding epitope on its antigen. Antibodies are polyvalent and so what is measured in practise is often the avidity of the antibody which is much greater. Click here to see an illustration of the difference between affinity and avidity |
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