title: The class-specific BCR tonic signal modulates lymphomagenesis in a c-myc deregulation transgenic model.
abstract: Deregulation of c-myc by translocation onto immunoglobulin (Ig) loci can promote B cell malignant proliferations with phenotypes as diverse as acute lymphoid leukemia, Burkitt lymphoma, diffuse large B cell lymphoma, myeloma... The B cell receptor (BCR) normally providing tonic signals for cell survival and mitogenic responses to antigens, can also contribute to lymphomagenesis upon sustained ligand binding or activating mutations. BCR signaling varies among cell compartments and BCR classes. For unknown reasons, some malignancies associate with expression of either IgM or class-switched Ig. We explored whether an IgA BCR, with strong tonic signaling, would affect lymphomagenesis in c-myc IgH 3'RR transgenic mice prone to lymphoproliferations. Breeding c-myc transgenics in a background where IgM expression was replaced with IgA delayed lymphomagenesis. By comparison to single c-myc transgenics, lymphomas from double mutant animals were more differentiated and less aggressive, with an altered transcriptional program. Larger tumor cells more often expressed CD43 and CD138, which culminated in a plasma cell phenotype in 10% of cases. BCR class-specific signals thus appear to modulate lymphomagenesis and may partly explain the observed association of specific Ig classes with human B cell malignancies of differential phenotype, progression and prognosis.
authors.affiliation: Centre National de la Recherche Scientifique, Limoges, France. Université de Limoges, Limoges, France. INSERM UMR U917, Rennes, France.
authors.forename: Rada
authors.initials: R
authors.lastname: Amin
authors.affiliation: Centre National de la Recherche Scientifique, Limoges, France.
authors.forename: Abdelghafour
authors.initials: A
authors.lastname: Marfak
authors.affiliation: INSERM UMR U917, Rennes, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Pangault
authors.affiliation: Centre National de la Recherche Scientifique, Limoges, France. Université de Limoges, Limoges, France.
authors.forename: Christelle
authors.initials: C
authors.lastname: Oblet
authors.affiliation: Centre National de la Recherche Scientifique, Limoges, France. Université de Limoges, Limoges, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Chanut
authors.affiliation: INSERM UMR U917, Rennes, France.
authors.forename: Karin
authors.initials: K
authors.lastname: Tarte
authors.affiliation: Centre National de la Recherche Scientifique, Limoges, France. Université de Limoges, Limoges, France.
authors.forename: Yves
authors.initials: Y
authors.lastname: Denizot
authors.affiliation: Centre National de la Recherche Scientifique, Limoges, France. Université de Limoges, Limoges, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Cogné
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000473:pathology; D002470:Cell Survival / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D006801:Humans; D007070:Immunoglobulin A / Q000235:genetics* / Q000276:immunology; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007075:Immunoglobulin M / Q000235:genetics* / Q000276:immunology; D051917:Leukosialin / Q000096:biosynthesis; D008223:Lymphoma / Q000235:genetics* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D011947:Receptors, Antigen, B-Cell / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology; D053668:Syndecan-1 / Q000096:biosynthesis
chemical_list: D007070:Immunoglobulin A; D007143:Immunoglobulin Heavy Chains; D007075:Immunoglobulin M; D051917:Leukosialin; C489428:Myc protein, mouse; D016271:Proto-Oncogene Proteins c-myc; D011947:Receptors, Antigen, B-Cell; C508242:Sdc1 protein, mouse; D053668:Syndecan-1