Oncotarget

Research Papers:

The class-specific BCR tonic signal modulates lymphomagenesis in a c-myc deregulation transgenic model

Rada Amin, Abdelghafour Marfak, Céline Pangault, Christelle Oblet, Aurélie Chanut, Karin Tarte, Yves Denizot and Michel Cogné _

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Oncotarget. 2014; 5:8995-9006. https://doi.org/10.18632/oncotarget.2297

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Abstract

Rada Amin1,2,3, Abdelghafour Marfak1 , Céline Pangault3, Christelle Oblet1,2, Aurélie Chanut1,2, Karin Tarte3, Yves Denizot1,2 and Michel Cogné1,2

1 Centre National de la Recherche Scientifique, Limoges, France 

2 Université de Limoges, Limoges, France 

3 INSERM UMR U917, Rennes, France

Correspondence:

Michel Cogné, email:

Keywords: BCR, c-myc, lymphoma, IgA, B cell

Received: June 09, 2014 Accepted: July 31, 2014 Published: July 31, 2014

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.


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