Class, or isotype, switching is the process whereby a B cell changes the heavy chain class of the antibody it synthesizes by changing the heavy chain constant (CH) region expressed, but not the light chain or heavy chain variable (VH) regions. The change in antibody class, except to IgE), is effected by a deletional DNA recombination event called switch recombination, which occurs between tandemly repeated sequences called switch regions. Switch recombination causes the recombined V (D) J gene segment, which is initially expressed with the Cu gene, to be subsequently expressed with one of six (mouse) or seven (human) downstream CH genes (Shimizu et al., 1982). IgE) is an exception, as it is coexpressed with IgM by the mechanisms of alternative RNA processing and termination of transcription (Knapp et al., 1982, Maki et al., 1981; Moore et al., 1981). Diagrams of the heavy chain gene loci in mouse and humans are shown in Fig. 1. Because antibody specificity is determined by the variable regions of antibodies, class switching does not change the antigen-binding specificity. Because effector functions of antibodies are determined by the CH regions, class switching does change the effector function of the antibody. Different Ig classes are found in most vertebrates examined, suggesting the importance of having different effector functions. There are five classes of immunoglobulins in mice, rats, and humans: IgM, Ig| D, IgG, IgE, and IgA. There are four subclasses of IgG (IgG1, IgG2b, IgG2a, and IgG3 in the mouse; IgG1, IgG2, IgG3, and IgG4 in human) and in human two subclasses of IgA, IgA1 and IgA2. The Cy genes appear to have duplicated since divergence of the ancestors to mice and humans; thus, there is an incomplete correspondence between the subclasses. Antibodies of different heavy chain classes differ in size, in vivo half-life, ability to bind to cell surface Fc receptors, ability to activate complement, sensitivity to digestion by proteolytic enzymes, and the tendency to aggregate (reviewed in Snapper and Finkelman, 1993). Two of the classes, IgM and IgA, form pentamers/hexamers and dimers/trimers/tetramers, respectively, when secreted, thus increasing their avidity. IgG3 tends to aggregate after binding antigen, also increasing its avidity (Greenspan and Cooper, 1992).