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.
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 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 class switch recombination 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 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.
Unité Mixte de Recherche Centre National de la Recherche Scientifique, Université de Limoges, 2 rue du Dr Marcland, Limoges Cedex, France.
Christelle
C
Vincent-Fabert
Remi
R
Fiancette
Eric
E
Pinaud
Véronique
V
Truffinet
Nadine
N
Cogné
Michel
M
Cogné
Yves
Y
Denizot
D000818:Animals; D017209:Apoptosis; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism; D002460:Cell Line; D049109:Cell Proliferation; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D017578:Immunoglobulin Class Switching / Q000235:genetics*; D007072:Immunoglobulin D / Q000235:genetics / Q000378:metabolism; D007143:Immunoglobulin Heavy Chains / Q000235:genetics* / Q000378:metabolism; D007132:Immunoglobulin Isotypes / Q000235:genetics / Q000378:metabolism; D007075:Immunoglobulin M / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D011995:Recombination, Genetic; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017384:Sequence Deletion; D014158:Transcription, Genetic
D007072:Immunoglobulin D; D007143:Immunoglobulin Heavy Chains; D007132:Immunoglobulin Isotypes; D007075:Immunoglobulin M