The IgH 3′ regulatory region governs μ chain transcription in mature B lymphocytes and the B cell fate

Abstract

// Alexis Saintamand 1 , Pauline Rouaud 1 , Armand Garot 1 , Faten Saad 1 , Claire Carrion 1 , Christelle Oblet 1 , Michel Cogné 1, 2, 3 , Eric Pinaud 1 , Yves Denizot 1 1 CNRS, CRIBL, UMR 7276, Limoges, France 2 Université de Limoges, CRIBL, UMR 7276, Limoges, France 3 Institut Universitaire de France, Paris, France Correspondence to: Yves Denizot, e-mail: yves.denizot@unilim.fr Keywords: BCR, B cell fate, IgH 3’ regulatory enhancers, knock-out mice Received: December 17, 2014      Accepted: December 21, 2014      Published: March 03, 2015 ABSTRACT We report that the IgH 3’ regulatory region (3’RR) has no role on μ chain transcription and pre-BCR expression in B cell progenitors. In contrast, analysis of heterozygous IgH a Δ3’RR /b wt mice indicated that the 3’RR controls μ chain transcripts in mature splenocytes and impacts membrane IgM density without obvious effect on BCR signals (colocalisation with lipid rafts and phosphorylation of Erk and Akt after BCR crosslinking). Deletion of the 3’RR modulates the B cell fate to less marginal zone B cells. In conclusion, the 3’RR is dispensable for pre-BCR expression and necessary for optimal commitments toward the marginal zone B cell fate. These results reinforce the concept of a dual regulation of the IgH locus transcription and accessibility by 5’ elements at immature B cell stages, and by the 3’RR as early as the resting mature B cell stage and then along further activation and differentiation.