title: Mice deficient for the type II topoisomerase-like DNA transesterase Spo11 show normal immunoglobulin somatic hypermutation and class switching.
abstract: Somatic hypermutation in B cells undergoing T cell dependent immune responses generates high affinity antibodies that provide protective immunity. B cells also switch from the expression of immunoglobulin (Ig) M and IgD to that of other Ig classes through somatic DNA recombination. Recent work has implicated DNA strand breaks, possibly DNA double strand breaks (DSB), as the initiating lesions in both class switch recombination and hypermutation, although the etiology of these lesions is not understood. Spo11, a protein structurally related to archaeal type II topoisomerases, generates DSB that initiate meiotic recombination. This characteristic, together with its expression pattern, marks this enzyme as a potential candidate for the initiation of hypermutation, and perhaps also for Ig class switching. To investigate whether Spo11 is involved in these processes, we studied the T cell dependent immune response of Spo11-deficient (Spo11(-/-)) mice against the hapten nitrophenyl (NP). We found that V186.2-bearing IgG1 transcripts had normal levels and patterns of somatic hypermutation. Furthermore, Spo11(-/-) mice showed normal serum levels of all Ig isotypes. These results indicate that Spo11 is not required for Ig hypermutation or class switch recombination.
authors.affiliation: Institute for Cancer Genetics, Columbia University, New York, USA.
authors.forename: Ulf
authors.initials: U
authors.lastname: Klein
authors.forename: Gloria
authors.initials: G
authors.lastname: Esposito
authors.forename: Frédéric
authors.initials: F
authors.lastname: Baudat
authors.forename: Scott
authors.initials: S
authors.lastname: Keeney
authors.forename: Maria
authors.initials: M
authors.lastname: Jasin
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D001483:Base Sequence; D004250:DNA Topoisomerases, Type II / Q000172:deficiency* / Q000235:genetics / Q000276:immunology*; D018076:DNA, Complementary / Q000235:genetics; D004706:Endodeoxyribonucleases; D004950:Esterases / Q000172:deficiency* / Q000235:genetics / Q000276:immunology*; D017578:Immunoglobulin Class Switching; D007132:Immunoglobulin Isotypes / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D027041:Somatic Hypermutation, Immunoglobulin; D000099257:Meiotic Recombination Protein SPO11
chemical_list: D004250:DNA Topoisomerases, Type II; D018076:DNA, Complementary; D004706:Endodeoxyribonucleases; D004950:Esterases; D007132:Immunoglobulin Isotypes; D012333:RNA, Messenger; D000099257:Meiotic Recombination Protein SPO11