title: DNA-dependent protein kinase activity is not required for immunoglobulin class switching.
abstract: Class switch recombination (CSR), similar to V(D)J recombination, is thought to involve DNA double strand breaks and repair by the nonhomologous end-joining pathway. A key component of this pathway is DNA-dependent protein kinase (DNA-PK), consisting of a catalytic subunit (DNA-PKcs) and a DNA-binding heterodimer (Ku70/80). To test whether DNA-PKcs activity is essential for CSR, we examined whether IgM(+) B cells from scid mice with site-directed H and L chain transgenes were able to undergo CSR. Although B cells from these mice were shown to lack DNA-PKcs activity, they were able to switch from IgM to IgG or IgA with close to the same efficiency as B cells from control transgenic and nontransgenic scid/+ mice, heterozygous for the scid mutation. We conclude that CSR, unlike V(D)J recombination, can readily occur in the absence of DNA-PKcs activity. We suggest nonhomologous end joining may not be the (primary or only) mechanism used to repair DNA breaks during CSR.
authors.affiliation: Institute for Cancer Research, Fox Chase Cancer Center, 7701 Burholme Avenue, Philadelphia, PA 19111, USA.
authors.forename: Gayle C
authors.initials: GC
authors.lastname: Bosma
authors.forename: Jiyoon
authors.initials: J
authors.lastname: Kim
authors.forename: Teresa
authors.initials: T
authors.lastname: Urich
authors.forename: Donna M
authors.initials: DM
authors.lastname: Fath
authors.forename: Maria G
authors.initials: MG
authors.lastname: Cotticelli
authors.forename: Norman R
authors.initials: NR
authors.lastname: Ruetsch
authors.forename: Marko Z
authors.initials: MZ
authors.lastname: Radic
authors.forename: Melvin J
authors.initials: MJ
authors.lastname: Bosma
mesh_terms: D000818:Animals; D001402:B-Lymphocytes; D004260:DNA Repair; D051747:DNA-Activated Protein Kinase; D004268:DNA-Binding Proteins; D005803:Genes, Immunoglobulin; D007108:Immune Tolerance; D007070:Immunoglobulin A / Q000096:biosynthesis; D017578:Immunoglobulin Class Switching; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000097:blood / Q000145:classification; D015847:Interleukin-4 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D011995:Recombination, Genetic; D013601:T-Lymphocytes / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000494:pharmacology
chemical_list: D004268:DNA-Binding Proteins; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D008070:Lipopolysaccharides; D016212:Transforming Growth Factor beta; D015847:Interleukin-4; D051747:DNA-Activated Protein Kinase; D017346:Protein Serine-Threonine Kinases