The Journal of Experimental Medicine
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Published online 25 April 2005 doi:10.1084/jem.20041988
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 201, Number 9, 1459-1466
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ARTICLE

 The 3' end of the heavy chain constant region locus enhances germline transcription and switch recombination of the four {gamma} genes

Wesley A. Dunnick, Jian Shi, Kevin A. Graves, and John T. Collins

Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109

CORRESPONDENCE Wesley Dunnick: wesadunn{at}umich.edu

The switch in immunoglobulin (Ig) heavy chain class is preceded by germline transcription and then mediated by a DNA recombination event. To study germline transcription and class switch recombination we used transgenic mice with a 230-kilobase bacterial artificial chromosome that included a rearranged VDJ gene and the entire heavy chain constant region locus. In addition to several lines with intact transgenes, we identified two lines in which the heavy chain locus transgene lacked C{alpha} and everything 3' of it, including the regulatory elements HS3a, HS1-2, HS3b, and HS4. B cells from both lines with the truncated transgenes make abundant transgenic (Tg) VDJCµ transcripts and IgM protein. Deletion of the 3' end of the locus results in dramatically reduced expression of both germline transcripts and switched VDJCH transcripts of the {gamma}3, {gamma}2b, {gamma}2a, and {varepsilon} genes. In addition, the transgenes lacking the 3' end of the locus express reduced amounts of {gamma}1 germline transcripts and 2–3% of the amount of Tg IgG1 in tissue culture compared with intact transgenes. Finally, switch recombination to {gamma}1 is undetectable in the transgenes lacking the 3' elements, as measured by digestion circularization–polymerase chain reaction or by the expression of VDJC{gamma}1 transcripts.

Abbreviations used: ARS, arsonate; DC, digestion circularization; End, endogenous; HPRT, hypoxanthine phosphoribsyl transferase; HS, hypersensitive; I, the 5' most exon of heavy chain germline transcripts; NTg, nonTg; S, switch region; Tg, transgenic.


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