title: The IgH 3' regulatory region influences lymphomagenesis in Igλ-Myc mice.
abstract: The IgH 3'regulatory region (3'RR), encompassing the four transcriptional enhancers hs3a-hs1,2-hs3b-hs4, has a key role on class switch recombination, somatic hypermutation, IgH transcription and B-cell fate. In plasma cells, transcribed IgH and IgL loci often colocalized in transcription factories and an IgL transcription defect might translate into lowered IgH transcription. We explored whether the 3'RR would affect lymphomagenesis in Igλ-Myc transgenic mice prone to lymphoproliferations. Breeding Igλ-Myc transgenics in a background deficient for the 3'RR influences lymphomagenesis toward less mature lymphomas (16% vs 54%, p = 0.01, Z test for two population proportions). In a 3'RR-deficient background mature tumors less often expressed the CD43 antigen (54% vs 0%, p = 0.02), a membrane glycoprotein expressed on activated mature B-cells. In contrast, in a 3'RR-deficient background tumors more often expressed the CD5 antigen (32% vs 12%, p = 0.05) that may serve to control autoimmunity and that is suspected to play a role in leukemic transformation. Lymphoma myc transcript levels, the Ki67 index of proliferation, the clonality, the usage of V(D)J segments, and their somatic hypermutation status were not affected in the 3'RR-deficient background. In conclusion, most probably through its action during the maturation process, the 3'RR can influence lymphomagenesis even when not linked with an oncogene.
authors.affiliation: CNRS UMR 7276, CRIBL, Université de Limoges, Limoges, France.
authors.forename: Faten
authors.initials: F
authors.lastname: Saad
authors.affiliation: CNRS UMR 7276, CRIBL, Université de Limoges, Limoges, France.
authors.forename: Alexis
authors.initials: A
authors.lastname: Saintamand
authors.affiliation: CNRS UMR 7276, CRIBL, Université de Limoges, Limoges, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Cogné
authors.affiliation: CNRS UMR 7276, CRIBL, Université de Limoges, Limoges, France.
authors.forename: Yves
authors.initials: Y
authors.lastname: Denizot
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D007143:Immunoglobulin Heavy Chains / Q000235:genetics* / Q000378:metabolism; D019394:Ki-67 Antigen / Q000032:analysis / Q000378:metabolism*; D008223:Lymphoma / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic
chemical_list: D007143:Immunoglobulin Heavy Chains; D019394:Ki-67 Antigen
keywords: B-cell lymphoma; IgH 3’ regulatory region; Igλ-Myc mice