NBME Immunology Practice Test

Switching the antibody isotype while keeping the same antigen specificity relies on class switch recombination. In activated B cells, the enzyme AID targets the switch regions upstream of the heavy-chain constant region genes and recombines them, moving from producing IgM (or IgD) to downstream constant regions like IgG, IgA, or IgE. This changes the antibody’s effector function and tissue distribution, not its antigen-binding site, because the variable region (which determines specificity) remains the same. Helper T cell signals through CD40-CD40L and cytokines such as IL-4, IFN-γ, and TGF-β direct which isotype is produced. Somatic hypermutation alters the variable region to increase affinity but does not change the isotype; receptor editing changes the light chain to alter specificity; clonal selection describes expansion of B cells after antigen binding.