IL-7R signaling activates widespread VH and DH gene usage to drive antibody diversity in bone marrow B cells.
Cell Rep
; 36(2): 109349, 2021 07 13.
Article
em En
| MEDLINE
| ID: mdl-34260907
ABSTRACT
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-7Rα-/- 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-7Rα-/- B cells. Thus, in addition to its roles in survival and proliferation, IL-7R signaling shapes the Igh repertoire by activating underpinning mechanisms.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Medula Óssea
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Região Variável de Imunoglobulina
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Linfócitos B
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Transdução de Sinais
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Receptores de Interleucina-7
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Genes de Cadeia Pesada de Imunoglobulina
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Diversidade de Anticorpos
Limite:
Animals
Idioma:
En
Revista:
Cell Rep
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Reino Unido