Sγ3 Switch Sequences Function in Place of Endogenous Sγ1 to Mediate Antibody Class Switching

Sγ3 Switch Sequences Function in Place of Endogenous Sγ1 to Mediate Antibody Class Switching

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Sγ3 Switch Sequences Function in Place of Endogenous Sγ1 to Mediate Antibody Class Switching

dc.contributor.author	Zarrin, Ali A.
dc.contributor.author	Goff, Peter H.
dc.contributor.author	Senger, Kate
dc.contributor.author	Alt, Frederick W.
dc.date.accessioned	2010-12-09T16:31:29Z
dc.date.issued	2008
dc.identifier.citation	Zarrin, Ali A., Peter H. Goff, Kate Senger, and Frederick W. Alt. 2008. Sγ3 switch sequences function in place of endogenous Sγ1 to mediate antibody class switching. The Journal of Experimental Medicine 205(7): 1567-1572.	en_US
dc.identifier.issn	0022-1007	en_US
dc.identifier.uri	http://nrs.harvard.edu/urn-3:HUL.InstRepos:4621710
dc.description.abstract	Immunoglobulin heavy chain (IgH) class switch recombination (CSR) replaces the initially expressed IgH Cμ exons with a set of downstream IgH constant region (CH) exons. Individual sets of CH exons are flanked upstream by long (1–10-kb) repetitive switch (S) regions, with CSR involving a deletional recombination event between the donor Sμ region and a downstream S region. Targeting CSR to specific S regions might be mediated by S region–specific factors. To test the role of endogenous S region sequences in targeting specific CSR events, we generated mutant B cells in which the endogenous 10-kb Sγ1 region was replaced with wild-type (WT) or synthetic 2-kb Sγ3 sequences or a synthetic 2-kb Sγ1 sequence. We found that both the inserted endogenous and synthetic Sγ3 sequences functioned similarly to a size-matched synthetic Sγ1 sequence to mediate substantial CSR to IgG1 in mutant B cells activated under conditions that stimulate IgG1 switching in WT B cells. We conclude that Sγ3 can function similarly to Sγ1 in mediating endogenous CSR to IgG1. The approach that we have developed will facilitate assays for IgH isotype–specific functions of other endogenous S regions.	en_US
dc.language.iso	en_US	en_US
dc.publisher	The Rockefeller University Press	en_US
dc.relation.isversionof	doi:10.1084/jem.20080451	en_US
dc.relation.hasversion	http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2442634/pdf/	en_US
dash.license	LAA
dc.title	Sγ3 Switch Sequences Function in Place of Endogenous Sγ1 to Mediate Antibody Class Switching	en_US
dc.type	Journal Article	en_US
dc.description.version	Version of Record	en_US
dc.relation.journal	The Journal of Experimental Medicine	en_US
dash.depositing.author	Alt, Frederick W.
dc.date.available	2010-12-09T16:31:29Z
dash.affiliation.other	HMS^Genetics	en_US
dash.affiliation.other	HMS^Pediatrics-Children's Hospital	en_US