First Author | Baizan-Edge A | Year | 2021 |
Journal | Cell Rep | Volume | 36 |
Issue | 2 | Pages | 109349 |
PubMed ID | 34260907 | Mgi Jnum | J:334259 |
Mgi Id | MGI:6874574 | Doi | 10.1016/j.celrep.2021.109349 |
Citation | Baizan-Edge A, et al. (2021) IL-7R signaling activates widespread VH and DH gene usage to drive antibody diversity in bone marrow B cells. Cell Rep 36(2):109349 |
abstractText | Generation of the primary antibody repertoire requires V(D)J recombination of hundreds of gene segments in the immunoglobulin heavy chain (Igh) locus. The role of interleukin-7 receptor (IL-7R) signaling in Igh recombination has been difficult to partition from its role in B cell survival and proliferation. With a detailed description of the Igh repertoire in murine IL-7Ralpha(-/-) bone marrow B cells, we demonstrate that IL-7R signaling profoundly influences VH gene selection during VH-to-DJH recombination. We find skewing toward 3' VH genes during de novo VH-to-DJH recombination more severe than the fetal liver (FL) repertoire and uncover a role for IL-7R signaling in DH-to-JH recombination. Transcriptome and accessibility analyses suggest reduced expression of B lineage transcription factors (TFs) and targets and loss of DH and VH antisense transcription in IL-7Ralpha(-/-) B cells. Thus, in addition to its roles in survival and proliferation, IL-7R signaling shapes the Igh repertoire by activating underpinning mechanisms. |