A striking feature of development and differentiation of the B-cell, which is a main player in the humoral immunity, is the involvement of a series of somatic alterations of genetic information. Each B cell expresses only a single antibody. The V(D)J rearrangement of the immunoglobulin heavy and light chain (IgH and IgL) variable-region genes determines the antigen specificity of the antibody. The class-switch recombination (CSR) in the IgH constant-region gene underlies the isotype switching from IgM to either IgG, IgE or IgA. Somatic hypermutation (SHM) of IgH and IgL variable region genes is important to generate high-affinity antibodies. In this lecture, we would like to discuss some milestone discoveries in the history of molecular immunology, in which Muramatsu et al., 2000 is an important achievement.