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

• Published in: Blood 2010-09, Vol.116 (11), p.1895-1898
• Main Authors: Vincent-Fabert, Christelle, Fiancette, Remi, Pinaud, Eric, Truffinet, Véronique, Cogné, Nadine, Cogné, Michel, Denizot, Yves
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; B-Lymphocytes - cytology; B-Lymphocytes - metabolism; Biological and medical sciences; Cell Line; Cell Proliferation; Cells, Cultured; Enzyme-Linked Immunosorbent Assay; Flow Cytometry; Fundamental and applied biological sciences. Psychology; Genic rearrangement. Recombination. Transposable element; Hematologic and hematopoietic diseases; Immunoglobulin Class Switching - genetics; Immunoglobulin D - genetics; Immunoglobulin D - metabolism; Immunoglobulin Heavy Chains - genetics; Immunoglobulin Heavy Chains - metabolism; Immunoglobulin Isotypes - genetics; Immunoglobulin Isotypes - metabolism; Immunoglobulin M - genetics; Immunoglobulin M - metabolism; Immunology; Life Sciences; Medical sciences; Mice; Mice, Inbred Strains; Mice, Knockout; Molecular and cellular biology; Molecular genetics; Recombination, Genetic; Regulatory Sequences, Nucleic Acid - genetics; Reverse Transcriptase Polymerase Chain Reaction; Sequence Deletion; Transcription, Genetic
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2010-01-264689

The immunoglobulin heavy chain locus (IgH) undergoes multiple changes along B-cell differentiation. In progenitor B cells, V(D)J assembly allows expression of µ heavy chains. In mature B cells, class switch recombination may replace the expressed constant (C)µ gene with a downstream CH 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 class switch recombination to all CH genes. Although plasma cell numbers are unaffected, we reveal the role of the 3′RR into the transcriptional burst normally associated with 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.