Genomic deletion of the whole IgH 3' regulatory region (hs3a, hs1,2, hs3b, hs4) dramatically affects class switch recombination and Ig secretion to all isotypes.

Christelle Vincent-Fabert (1) , Rémi Fiancette (1) , Eric Pinaud (1) , Véronique Truffinet (1) , Nadine Cogné (1) , Michel Cogné (1, 2) , Yves Denizot (1)

1 PMRIL - Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations
2 UNILIM - Université de Limoges

The immunoglobulin heavy chain locus (IgH) undergoes multiple changes along B-cell differentiation. In progenitor B-cells, V(D)J assembly allows expression of mu heavy chains. In mature B-cells, class switch recombination (CSR) may replace the expressed constant (C)mu gene with a downstream C(H) gene. Finally, plasma cell differentiation strongly boosts IgH transcription. How the multiple IgH transcriptional enhancers tune these changes is unclear. Here we demonstrate that deletion of the whole IgH 3' regulatory region (3'RR) allows normal maturation until the stage of IgM/IgD expressing lymphocytes, but nearly abrogates CSR to all C(H) genes. Although plasma cell numbers are unaffected, we reveal the role of the 3'RR into the transcriptional burst normally associated to plasma cell differentiation. Our study shows that transcriptional changes and recombinations occurring after antigen-encounter appear mainly controlled by the 3'RR working as a single functional unit.

Domaines: Immunologie

Christelle Vincent-Fabert, Rémi Fiancette, Eric Pinaud, Véronique Truffinet, Nadine Cogné, et al.. Genomic deletion of the whole IgH 3' regulatory region (hs3a, hs1,2, hs3b, hs4) dramatically affects class switch recombination and Ig secretion to all isotypes.. Blood, 2010, epub ahead of print. ⟨10.1182/blood-2010-01-264689⟩. ⟨hal-00514236⟩