Sgamma3 switch sequences function in place of endogenous Sgamma1 to mediate antibody class switching.
Immunoglobulin heavy chain (IgH) class switch recombination (CSR) replaces the initially expressed IgH Cmu exons with a set of downstream IgH constant region (C(H)) exons. Individual sets of C(H) exons are flanked upstream by long (1-10-kb) repetitive switch (S) regions, with CSR involving a deletional recombination event between the donor Smu 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 Sgamma1 region was replaced with wild-type (WT) or synthetic 2-kb Sgamma3 sequences or a synthetic 2-kb Sgamma1 sequence. We found that both the inserted endogenous and synthetic Sgamma3 sequences functioned similarly to a size-matched synthetic Sgamma1 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 Sgamma3 can function similarly to Sgamma1 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.
Department of Genetics, Howard Hughes Medical Institute, Children's Hospital, Immune Disease Institute, Harvard University Medical School, Boston, MA 02115, USA.
Ali A
AA
Zarrin
Peter H
PH
Goff
Kate
K
Senger
Frederick W
FW
Alt
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain / Q000235:genetics* / Q000276:immunology; D007127:Immunoglobulin Constant Regions / Q000235:genetics* / Q000276:immunology; D007143:Immunoglobulin Heavy Chains / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation / Q000276:immunology; D011995:Recombination, Genetic / Q000276:immunology
D007127:Immunoglobulin Constant Regions; D007143:Immunoglobulin Heavy Chains