TY - JOUR
T1 - Class-switch recombination in the absence of the igh 39 regulatory region
AU - Kim, Ahrom
AU - Han, Li
AU - Santiago, Gabriel E.
AU - Verdun, Ramiro E.
AU - Yu, Kefei
N1 - Publisher Copyright:
© 2016 by The American Association of Immunologists, Inc.
Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2016/10/1
Y1 - 2016/10/1
N2 - The ∼28-kb 39 regulatory region (39RR), which is located at the most distal 39 region of the Ig H chain locus, has multiple regulatory functions that control IgH expression, class-switch recombination (CSR), and somatic hypermutation. In this article, we report that deletion of the entire 39RR in a mouse B cell line that is capable of robust cytokine-dependent CSR to IgA results in reduced, but not abolished, CSR. These data suggest that 39RR is not absolutely required for CSR and, thus, is not essential for targeting activation-induced cytidine deaminase to S regions, as was suggested. Moreover, replacing 39RR with a DNA fragment including only its four DNase I hypersensitive sites (lacking the large spacer regions) restores CSR to a level equivalent to or even higher than in wild-Type cells, suggesting that the four hypersensitive sites contain most of the CSR-promoting functions of 39RR. Stimulated cells express abundant germline transcripts, with the presence or absence of 39RR, providing evidence that 39RR has a role in promoting CSR that is unique from enhancing S region transcription. The Journal of Immunology, 2016, 197: 2930-2935.
AB - The ∼28-kb 39 regulatory region (39RR), which is located at the most distal 39 region of the Ig H chain locus, has multiple regulatory functions that control IgH expression, class-switch recombination (CSR), and somatic hypermutation. In this article, we report that deletion of the entire 39RR in a mouse B cell line that is capable of robust cytokine-dependent CSR to IgA results in reduced, but not abolished, CSR. These data suggest that 39RR is not absolutely required for CSR and, thus, is not essential for targeting activation-induced cytidine deaminase to S regions, as was suggested. Moreover, replacing 39RR with a DNA fragment including only its four DNase I hypersensitive sites (lacking the large spacer regions) restores CSR to a level equivalent to or even higher than in wild-Type cells, suggesting that the four hypersensitive sites contain most of the CSR-promoting functions of 39RR. Stimulated cells express abundant germline transcripts, with the presence or absence of 39RR, providing evidence that 39RR has a role in promoting CSR that is unique from enhancing S region transcription. The Journal of Immunology, 2016, 197: 2930-2935.
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U2 - 10.4049/jimmunol.1600530
DO - 10.4049/jimmunol.1600530
M3 - Article
C2 - 27559052
AN - SCOPUS:84989827183
VL - 197
SP - 2930
EP - 2935
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 7
ER -