{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T23:29:38Z","timestamp":1790897378033,"version":"4.1.0"},"reference-count":73,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2009,1,1]],"date-time":"2009-01-01T00:00:00Z","timestamp":1230768000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2009,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The RecQ family helicase BLM is critically involved in the maintenance of genomic stability, and BLM mutation causes the heritable disorder Bloom\u2019s syndrome. Affected individuals suffer from a predisposition to a multitude of cancer types and an ill-defined immunodeficiency involving low serum Ab titers. To investigate its role in B cell biology, we inactivated murine Blm specifically in B lymphocytes in vivo. Numbers of developing B lymphoid cells in the bone marrow and mature B cells in the periphery were drastically reduced upon Blm inactivation. Of the major peripheral B cell subsets, B1a cells were most prominently affected. In the sera of Blm-deficient naive mice, concentrations of all Ig isotypes were low, particularly IgG3. Specific IgG Ab responses upon immunization were poor and mutant B cells exhibited a generally reduced Ab class switch capacity in vitro. We did not find evidence for a crucial role of Blm in the mechanism of class switch recombination. However, a modest shift toward microhomology-mediated switch junction formation was observed in Blm-deficient B cells. Finally, a cohort of p53-deficient, conditional Blm knockout mice revealed an increased propensity for B cell lymphoma development. Impaired cell cycle progression and survival as well as high rates of chromosomal structural abnormalities in mutant B cell blasts were identified as the basis for the observed effects. Collectively, our data highlight the importance of BLM-dependent genome surveillance for B cell immunity by ensuring proper development and function of the various B cell subsets while counteracting lymphomagenesis.<\/jats:p>","DOI":"10.4049\/jimmunol.182.1.347","type":"journal-article","created":{"date-parts":[[2014,4,18]],"date-time":"2014-04-18T19:17:12Z","timestamp":1397848632000},"page":"347-360","source":"Crossref","is-referenced-by-count":36,"title":["Genomic Instability Resulting from Blm Deficiency Compromises Development, Maintenance, and Function of the B Cell Lineage"],"prefix":"10.1093","volume":"182","author":[{"given":"Holger","family":"Babbe","sequence":"first","affiliation":[{"name":"Department of Genetics, Harvard Medical School , Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"McMenamin","sequence":"additional","affiliation":[{"name":"Department of Genetics, Harvard Medical School , Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elias","family":"Hobeika","sequence":"additional","affiliation":[{"name":"Max Planck Institute for Immunobiology and Centre for Biological Signalling Studies, Faculty of Biology, Albert-Ludwigs University of Freiburg , Freiburg,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Wang","sequence":"additional","affiliation":[{"name":"Immune Disease Institute, Harvard Medical School , Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott J","family":"Rodig","sequence":"additional","affiliation":[{"name":"Department of Pathology, Brigham & Women\u2019s Hospital , Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Reth","sequence":"additional","affiliation":[{"name":"Max Planck Institute for Immunobiology and Centre for Biological Signalling Studies, Faculty of Biology, Albert-Ludwigs University of Freiburg , Freiburg,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip","family":"Leder","sequence":"additional","affiliation":[{"name":"Department of Genetics, Harvard Medical School , Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2009,1,1]]},"reference":[{"key":"2026012806235705600_R1","first-page":"196","article-title":"Chromosomal stability and the DNA double-stranded break connection.","volume-title":"Nat. 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J.","year":"2003"},{"key":"2026012806235705600_R6","first-page":"870","article-title":"The Bloom\u2019s syndrome helicase suppresses crossing over during homologous recombination.","volume-title":"Nature","year":"2003"},{"key":"2026012806235705600_R7","first-page":"393","article-title":"Bloom syndrome: a mendelian prototype of somatic mutational disease.","volume-title":"Medicine","year":"1993"},{"key":"2026012806235705600_R8","first-page":"100","article-title":"Bloom\u2019s syndrome, XX: the first 100 cancers.","volume-title":"Cancer Genet. Cytogenet.","year":"1997"},{"key":"2026012806235705600_R9","first-page":"86","article-title":"Long-term study of the immunodeficiency of Bloom\u2019s syndrome.","volume-title":"Acta Paediatr.","year":"1992"},{"key":"2026012806235705600_R10","first-page":"1089","article-title":"Bloom\u2019s syndrome: clinical features and immunologic abnormalities of four patients.","volume-title":"Am. J. Dis. 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Biol.","year":"2007"},{"key":"2026012806235705600_R29","first-page":"6713","article-title":"Mutation of the murine Bloom\u2019s syndrome gene produces global genome destabilization.","volume-title":"Mol. Cell. Biol.","year":"2006"},{"key":"2026012806235705600_R30","first-page":"1387","article-title":"Chromosome instability and tumor predisposition inversely correlate with BLM protein levels.","volume-title":"DNA Repair","year":"2003"},{"key":"2026012806235705600_R31","first-page":"13789","article-title":"Testing gene function early in the B cell lineage in mb1-cre mice.","volume-title":"Proc. Natl. Acad. Sci. USA","year":"2006"},{"key":"2026012806235705600_R32","first-page":"215","article-title":"Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours.","volume-title":"Nature","year":"1992"},{"key":"2026012806235705600_R33","first-page":"253","article-title":"Origins and functions of B-1 cells with notes on the role of CD5.","volume-title":"Annu. Rev. 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Immunol.","year":"1994"},{"key":"2026012806235705600_R39","first-page":"14553","article-title":"Switch junction sequences in PMS2-deficient mice reveal a microhomology-mediated mechanism of Ig class switch recombination.","volume-title":"Proc. Natl. Acad. Sci. USA","year":"2001"},{"key":"2026012806235705600_R40","first-page":"365","article-title":"DNA sequences at immunoglobulin switch region recombination sites.","volume-title":"Nucleic Acids Res.","year":"1993"},{"key":"2026012806235705600_R41","first-page":"4781","article-title":"The bulk of the peripheral B-cell pool in mice is stable and not rapidly renewed from the bone marrow.","volume-title":"Proc. Natl. Acad. Sci. USA","year":"1990"},{"key":"2026012806235705600_R42","first-page":"20105","article-title":"VDJ recombination in ataxia telangiectasia, Bloom\u2019s syndrome, and a DNA ligase I-associated immunodeficiency disorder.","volume-title":"J. Biol. 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Biol.","year":"2004"},{"key":"2026012806235705600_R47","first-page":"758","article-title":"A retarded rate of DNA chain growth in Bloom\u2019s syndrome.","volume-title":"Proc. Natl. Acad. Sci. USA","year":"1975"},{"key":"2026012806235705600_R48","first-page":"3141","article-title":"An abnormal profile of DNA replication intermediates in Bloom\u2019s syndrome.","volume-title":"Cancer Res.","year":"1990"},{"key":"2026012806235705600_R49","first-page":"35","article-title":"RecQ helicases and cellular responses to DNA damage.","volume-title":"Mutat. Res.","year":"2002"},{"key":"2026012806235705600_R50","first-page":"1210","article-title":"BLM helicase-dependent transport of p53 to sites of stalled DNA replication forks modulates homologous recombination.","volume-title":"EMBO J.","year":"2003"},{"key":"2026012806235705600_R51","first-page":"22839","article-title":"The Bloom\u2019s syndrome helicase can promote the regression of a model replication fork.","volume-title":"J. Biol. 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Immunol.","year":"2003"},{"key":"2026012806235705600_R57","first-page":"547","article-title":"Abnormal development and function of B lymphocytes in mice deficient for the signaling adaptor protein SLP-65.","volume-title":"Immunity","year":"1999"},{"key":"2026012806235705600_R58","first-page":"39","article-title":"Abnormal B lymphocyte development, activation, and differentiation in mice that lack or overexpress the CD19 signal transduction molecule.","volume-title":"Immunity","year":"1995"},{"key":"2026012806235705600_R59","first-page":"1111","article-title":"Immunoglobulin class switch recombination is impaired in Atm-deficient mice.","volume-title":"J. Exp. Med.","year":"2004"},{"key":"2026012806235705600_R60","first-page":"459","article-title":"53BP1 is required for class switch recombination.","volume-title":"J. Cell Biol.","year":"2004"},{"key":"2026012806235705600_R61","first-page":"30515","article-title":"Functional link between BLM defective in Bloom\u2019s syndrome and the ataxia-telangiectasia-mutated protein, ATM.","volume-title":"J. Biol. Chem.","year":"2002"},{"key":"2026012806235705600_R62","first-page":"1103","article-title":"ATM is required for efficient recombination between immunoglobulin switch regions.","volume-title":"J. Exp. Med.","year":"2004"},{"key":"2026012806235705600_R63","first-page":"2306","article-title":"Molecular genetics of RecQ helicase disorders.","volume-title":"Cell. Mol. Life Sci.","year":"2007"},{"key":"2026012806235705600_R64","first-page":"8437","article-title":"Telomere shortening exposes functions for the mouse Werner and Bloom syndrome genes.","volume-title":"Mol. Cell. 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