Class Switching of Heavy Chains
As mentioned before, the first detectable antibody synthesized in response to an antigen is IgM. Later, the other classes, IgM, IgD, IgG, IgE, and IgA can be detected. Remarkably, myelomas in culture also can switch the class of antibody they are synthesizing, but without changing the antigen specificity.
Since the class of an antibody is determined solely by the constant region of the heavy chain, class switching must be generated by a change in the C segment that is connected to the V, D, and J segments.
As mentioned above, following the J segment, the chromosome contains a series of C region segments beginning with the one coding for the M class of immunoglobulin. This array of eight C region segments is spread over 200 Kb of DNA and possesses an order consistent with the sequence of class switching that has been observed. Class switching replaces one of the downstream C regions for the M constant region by deleting intervening DNA. Hence, the intervening sequence between the J and C region and sites ahead of the other C region genes contain signals used in the generation of the deletions that produce class switching.