The Journal of Experimental Medicine
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Published online 15 January 2001.
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© The Rockefeller University Press, 0022-1007/2001/1/159/ $5.00
The Journal of Experimental Medicine, Volume 193, Number 2, January 15, 2001 159-168

Original Article

The µ Switch Region Tandem Repeats Are Important, but Not Required, for Antibody Class Switch Recombination

Thomas M. Lubya, Carol E. Schraderb, Janet Stavnezerb, and Erik Selsinga

a Department of Pathology, Program in Immunology, Sackler School of Biomedical Sciences, Tufts University School of Medicine, Boston, Massachusetts 02111
b Department of Molecular Genetics and Microbiology, Program in Immunology and Virology, University of Massachusetts Medical School, Worcester, Massachusetts 01655
Department of Pathology, Tufts University School of Medicine, Boston, MA 02111.617-636-6903617-636-0467

eselsing{at}opal.tufts.edu

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 (Sµ) from the murine µ H chain gene. We find that the Sµ 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 Sµ tandem repeats must be capable of directing the class switch mechanism. The maintenance of the highly repeated Sµ element during evolution appears to reflect selection for a highly efficient switching process rather than selection for a required sequence element.

Key Words: gene rearrangement • B lymphocyte • heavy chain • class switching • immunoglobulin isotype

Abbreviations used in this paper: Ach, acetylcholine; Ars, p-phenylarsonate; DC, digestion circularization; NHEJ, nonhomologous end joining; S, switch.

© 2001 The Rockefeller University Press


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