Heavy - Chain Class Switch Does Not Terminate

the Ig loci undergo several molecular events. The somatic hypermutation mechanism is induced, causing somatic mutations to accumulate in and around the V regions at the average rate of ti10-3/bp/div (1, 2) . Later, this mechanism is turned off, as mutation rates drop sharply to <10 -5/ by/div and perhaps as low as <5 x 10-$/bp/div. (3-5) . The IgH constant region undergoes deletional rearrangement mediated by repetitive "switch region" DNA sequences located 5' of constant region exons. This results in a switch of the constant region that is juxtaposed to the VDJ complex (6, 7), to a different H-chain isotype . Because of an apparent temporal correlation of hypermutation and isotype switch (3, 8, 9), it has been proposed that they are developmentally and/or mechanistically related processes . The initial proposal that mutation does not occur until after isotype switch (9), was disproved by the findings ofmutated IgM antibodies (4, 10, 11) . A more recent proposal, based on the finding that mutation stops (3-5) and the finding of identically switched/identically mutated cells (3), is that hypermutation stops after class switch (12, 13) . Moreover, it was proposed that the deletion of the C/A gene on the expressed allele was involved in the mechanism of cessation of hypermutation (12) . In this paper we test this latter hypothesis and discuss the implications of our findings for models of B cell development and mechanisms of class switch and somatic mutation .