The Eμ enhancer region influences H chain expression and B cell fate without impacting IgVH repertoire and immune response in vivo. - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Journal of Immunology Année : 2014

The Eμ enhancer region influences H chain expression and B cell fate without impacting IgVH repertoire and immune response in vivo.

Résumé

The IgH intronic enhancer region Eμ is a combination of both a 220-bp core enhancer element and two 310-350-bp flanking scaffold/matrix attachment regions named MARsEμ. In the mouse, deletion of the core-enhancer Eμ element mainly affects VDJ recombination with minor effects on class switch recombination. We carried out endogenous deletion of the full-length Eμ region (core plus MARsEμ) in the mouse genome to study VH gene repertoire and IgH expression in developing B-lineage cells. Despite a severe defect in VDJ recombination with partial blockade at the pro-B cell stage, Eμ deletion (core or full length) did not affect VH gene usage. Deletion of this regulatory region induced both a decrease of pre-B cell and newly formed B cell compartments and a strong orientation toward the marginal zone B cell subset. Because Igμ H chain expression was decreased in Eμ-deficient pre-B cells, we propose that modification of B cell homeostasis in deficient animals was caused by "weak" pre-B cell and BCR expression. Besides imbalances in B cell compartments, Ag-specific Ab responses were not impaired in animals carrying the Eμ deletion. In addition to its role in VDJ recombination, our study points out that the full-length Eμ region does not influence VH segment usage but ensures efficient Igμ-chain expression required for strong signaling through pre-B cells and newly formed BCRs and thus participates in B cell inflow and fate.

Domaines

Immunologie

Dates et versions

hal-01110453 , version 1 (28-01-2015)

Identifiants

Citer

Marie Marquet, Armand Garot, Sébastien Bender, Claire Carrion, Pauline Rouaud, et al.. The Eμ enhancer region influences H chain expression and B cell fate without impacting IgVH repertoire and immune response in vivo.. Journal of Immunology, 2014, 193 (3), pp.1171-83. ⟨10.4049/jimmunol.1302868⟩. ⟨hal-01110453⟩
64 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More