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

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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

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