Mice deficient for the type II topoisomerase-like DNA transesterase Spo11 show normal immunoglobulin somatic hypermutation and class switching Journal Article

  

Authors:	Klein, U.; Esposito, G.; Baudat, F.; Keeney, S.; Jasin, M.
Article 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 (lg) M and lgD to that of other lg 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 lg 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 lgG1 transcripts had normal levels and patterns of somatic hypermutation. Furthermore, Spo11-/- mice showed normal serum levels of all lg isotypes. These results indicate that Spo11 is not required for lg hypermutation or class switch recombination.
Keywords:	controlled study; protein expression; unclassified drug; somatic mutation; nonhuman; t lymphocyte; animal cell; dna recombination; mouse; meiosis; animals; mice; mice, knockout; mice, inbred c57bl; b lymphocyte; b-lymphocytes; dna strand breakage; somatic hypermutation; dna; double stranded dna; gene rearrangement; immunoglobulin gene; immunoglobulin g; rna, messenger; antibody response; base sequence; immunity; immunoglobulin g1; immunoglobulin class switching; protein structure; dna topoisomerase (atp hydrolysing); antibody; antibody production; antibody affinity; spo11 protein; dna topoisomerases, type ii, eukaryotic; esterases; dna, complementary; immunoglobulin m; enzyme deficiency; dna double strand breaks; somatic hypermutation, immunoglobulin; archaeal protein; immunoglobulin class; priority journal; article; ig class switching; spo11 transesterase; dinitrophenylhapten; immunoglobulin isotypes
Journal Title:	European Journal of Immunology
Volume:	32
Issue:	2
ISSN:	0014-2980
Publisher:	Wiley V C H Verlag Gmbh
Date Published:	2002-02-01
Start Page:	316
End Page:	321
Language:	English
DOI:	10.1002/1521-4141(200202)32:2<316::aid-immu316>3.0.co;2-p
PUBMED:	11807770
PROVIDER:	scopus
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-0036178823&partnerID=40&md5=a0645bdcffcca4f80258bd6838c9dd5b
Notes:	Export Date: 14 November 2014 -- Source: Scopus

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