Abstract:
:As a master regulator of functional Ig heavy chain (IgH) expression, the IgH 3' regulatory region (3'RR) controls multiple transcription events at various stages of B-cell ontogeny, from newly formed B cells until the ultimate plasma cell stage. The IgH 3'RR plays a pivotal role in early B-cell receptor expression, germ-line transcription preceding class switch recombination, interactions between targeted switch (S) regions, variable region transcription before somatic hypermutation, and antibody heavy chain production, but the functional ranking of its different elements is still inaccurate, especially that of its evolutionarily conserved quasi-palindromic structure. By comparing relevant previous knockout (KO) mouse models (3'RR KO and hs3b-4 KO) to a novel mutant devoid of the 3'RR quasi-palindromic region (3'PAL KO), we pinpointed common features and differences that specify two distinct regulatory entities acting sequentially during B-cell ontogeny. Independently of exogenous antigens, the 3'RR distal part, including hs4, fine-tuned B-cell receptor expression in newly formed and naïve B-cell subsets. At mature stages, the 3'RR portion including the quasi-palindrome dictated antigen-dependent locus remodeling (global somatic hypermutation and class switch recombination to major isotypes) in activated B cells and antibody production in plasma cells.
journal_name
Proc Natl Acad Sci U S Aauthors
Garot A,Marquet M,Saintamand A,Bender S,Le Noir S,Rouaud P,Carrion C,Oruc Z,Bébin AG,Moreau J,Lebrigand K,Denizot Y,Alt FW,Cogné M,Pinaud Edoi
10.1073/pnas.1514090113subject
Has Abstractpub_date
2016-02-09 00:00:00pages
1618-23issue
6eissn
0027-8424issn
1091-6490pii
1514090113journal_volume
113pub_type
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