The mu switch region tandem repeats are important, but not required, for antibody class switch recombination.

Abstract

Class switch DNA recombinations change the constant (C) region of the antibody heavy (H) chain expressed by a B cell and thereby change the antibody effector function. Unusual tandemly repeated sequence elements located upstream of H chain gene exons have long been thought to be important in the targeting and/or mechanism of the switch recombination process. We have deleted the entire switch tandem repeat element (S(mu)) from the murine (mu) H chain gene. We find that the S(mu) tandem repeats are not required for class switching in the mouse immunoglobulin H-chain locus, although the efficiency of switching is clearly reduced. Our data demonstrate that sequences outside of the S(mu) tandem repeats must be capable of directing the class switch mechanism. The maintenance of the highly repeated S(mu) element during evolution appears to reflect selection for a highly efficient switching process rather than selection for a required sequence element.