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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.

Abstract : 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.
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https://hal.archives-ouvertes.fr/hal-00514236
Contributor : Claire Carrion Connect in order to contact the contributor
Submitted on : Wednesday, September 1, 2010 - 4:54:42 PM
Last modification on : Tuesday, October 19, 2021 - 11:13:09 AM

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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, American Society of Hematology, 2010, epub ahead of print. ⟨10.1182/blood-2010-01-264689⟩. ⟨hal-00514236⟩

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