The {micro} Switch Region Tandem Repeats Are Important, but Not Required, for Antibody Class Switch Recombination

doi:10.1084/jem.193.2.159

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. Luby^a, Carol E. Schrader^b, Janet Stavnezer^b, and Erik Selsing^a

^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) regionof the antibody heavy (H) chain expressed by a B cell and therebychange the antibody effector function. Unusual tandemly repeatedsequence elements located upstream of H chain gene exons havelong been thought to be important in the targeting and/or mechanismof the switch recombination process. We have deleted the entireswitch tandem repeat element (Sµ) from the murine µH chain gene. We find that the Sµ tandem repeats are notrequired for class switching in the mouse immunoglobulin H-chainlocus, although the efficiency of switching is clearly reduced.Our data demonstrate that sequences outside of the Sµtandem repeats must be capable of directing the class switchmechanism. The maintenance of the highly repeated Sµ elementduring evolution appears to reflect selection for a highly efficientswitching process rather than selection for a required sequenceelement.

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.

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