hypermutation
Summary
Hypermutation (somatic hypermutation) is a very high rate of point mutations in the variable-region genes of antibodies in activated B cells. Selection of the B cells whose mutated antibodies bind antigen more tightly produces affinity maturation.
Detail
Meaning: After a B cell meets antigen and receives help from a T helper cell, it divides in a germinal center of a lymph node. As it divides, the DNA for the variable regions of the heavy and light chains collects point mutations at a rate far above the rest of the genome. Most changes do nothing or weaken binding; a few strengthen it. B cells with tighter binding compete better for antigen and survive, so average affinity rises over repeated rounds (affinity maturation).
On the MCAT: Passages compare primary and secondary responses, or antibody sequences early and late in an infection. Expect mutations mainly in variable, not constant, regions; mutations in B cell DNA that are not inherited by offspring; and rising affinity through selection. It is often set against V(D)J recombination, which builds the initial diversity before antigen exposure.
Common confusion: The mutations themselves are random and do not raise affinity; selection of the better binders does. Hypermutation is also not class switching, which changes the constant region (the isotype) but leaves the antigen-binding site the same.
Sources
- Campbell Biology
- Janeway's Immunobiology
Written for the MCAT and checked before it was published. For study reference only. Spotted an error? Let us know.