The Eλ3–1 enhancer is essential for V(D)J recombination of the murine immunoglobulin lambda light chain locus

Haque, Syeda F.Y.; Bevington, Sarah L; Boyes, Joan

doi:10.1016/j.bbrc.2013.10.087

Cited by 7 publications

(4 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This also holds true for B-KO mice. The current model proposes that this preference results from the cooperative function of the λ 1-3 and λ 2-4 enhancers, which surround the Igl-V -gene segments 3’ and 5’ of the λ1 and λ3 family and are bound by the same transcription factors ( Collins and Watson, 2018 ; Haque et al, 2013 ). The distance of the λ 2-4 enhancer to the λ 1-3 enhancer might preclude that Igl gene recombination 5’ of the λ 2-4 enhancer profit from transcription factors and co-factors of the recombination machinery bound to the λ 1-3 enhancer.…”

Section: Discussionmentioning

confidence: 99%

Kidins220 regulates the development of B cells bearing the λ light chain

Schaffer,

Fiala,

Hils

et al. 2024

eLife

View full text Add to dashboard Cite

The ratio between κ and λ light chain (LC)-expressing B cells varies considerably between species. We recently identified Kinase D-interacting substrate of 220 kDa (Kidins220) as an interaction partner of the BCR. In vivo ablation of Kidins220 in B cells resulted in a marked reduction of λLC-expressing B cells. Kidins220 knockout B cells fail to open and recombine the genes of the Igl locus, even in genetic scenarios where the Igk genes cannot be rearranged or where the κLC confers autoreactivity. Igk gene recombination and expression in Kidins220-deficient B cells is normal. Kidins220 regulates the development of λLC B cells by enhancing the survival of developing B cells and thereby extending the time-window in which the Igl locus opens and the genes are rearranged and transcribed. Further, our data suggest that Kidins220 guarantees optimal pre-BCR and BCR signaling to induce Igl locus opening and gene recombination during B cell development and receptor editing.

show abstract

Section: Discussionmentioning

confidence: 99%

Kidins220 regulates the development of B cells bearing the λ light chain

Schaffer,

Fiala,

Hils

et al. 2024

eLife

View full text Add to dashboard Cite

show abstract

“…This also holds true for B-KO mice. The current model proposes that this preference results from the cooperative function of the λ 1-3 and λ 2-4 enhancers, which surround the Igλ V-gene segments 3’ and 5’ of the λ1 and λ3 family and are bound by the same transcription factors ( 74 , 75 ). The distance of the λ 2-4 enhancer to the λ 1-3 enhancer might preclude that λLC gene recombination 5’ of the λ 2-4 enhancer profit from transcription factors and co-factors of the recombination machinery bound to the λ1-3 enhancer.…”

Section: Discussionmentioning

confidence: 99%

Kidins220 regulates the development of B cells bearing the λ light chain

Schaffer

Fiala

Hils

et al. 2022

Preprint

View full text Add to dashboard Cite

The ratio between Igκ and Igλ light chain (LC)-expressing B cells varies considerably between species. We recently identified Kinase D-interacting substrate of 220 kDa (Kidins220) as an interaction partner of the BCR. In vivo ablation of Kidins220 in B cells resulted in a marked reduction of λLC-expressing B cells. Kidins220 knockout B cells fail to open and recombine the genes of the λLC locus, even in genetic scenarios where the κLC genes cannot be rearranged or where the κLC confers autoreactivity. κLC gene recombination and expression in Kidins220-deficient B cells is normal. Kidins220 regulates the development of λLC B cells by enhancing the survival of developing B cells and thereby extending the time-window in which the λLC locus opens and the genes are rearranged and transcribed. Further, our data suggest that Kidins220 guarantees optimal pre-BCR and BCR signaling to induce λLC locus opening and gene recombination during B cell development and receptor editing.One Sentence SummaryWe demonstrate that the scaffold protein Kidins220 regulates the development of λLC B cells by supporting B cell precursor survival and optimizing pre-BCR and BCR signaling to open, recombine, and transcribe the genes of the λLC locus.

show abstract

“…Rearrangements are initiated in the kappa locus and in case they are non-productive, the lambda locus is activated. Similar to IGH and IGK loci, rearrangements and expression of IGL genes are also regulated by enhancers [218,219]. There are marked differences between the murine and human IGL enhancers.…”

Section: Structure and Function Of Lgk And Igl Enhancers In Normal B Cellsmentioning

confidence: 99%

Enhancing B-Cell Malignancies—On Repurposing Enhancer Activity towards Cancer

Kasprzyk

Sura

Dzikiewicz‐Krawczyk

2021

Cancers

View full text Add to dashboard Cite

B-cell lymphomas and leukemias derive from B cells at various stages of maturation and are the 6th most common cancer-related cause of death. While the role of several oncogenes and tumor suppressors in the pathogenesis of B-cell neoplasms was established, recent research indicated the involvement of non-coding, regulatory sequences. Enhancers are DNA elements controlling gene expression in a cell type- and developmental stage-specific manner. They ensure proper differentiation and maturation of B cells, resulting in production of high affinity antibodies. However, the activity of enhancers can be redirected, setting B cells on the path towards cancer. In this review we discuss different mechanisms through which enhancers are exploited in malignant B cells, from the well-studied translocations juxtaposing oncogenes to immunoglobulin loci, through enhancer dysregulation by sequence variants and mutations, to enhancer hijacking by viruses. We also highlight the potential of therapeutic targeting of enhancers as a direction for future investigation.

show abstract

The Eλ3–1 enhancer is essential for V(D)J recombination of the murine immunoglobulin lambda light chain locus

Cited by 7 publications

References 23 publications

Kidins220 regulates the development of B cells bearing the λ light chain

Kidins220 regulates the development of B cells bearing the λ light chain

Kidins220 regulates the development of B cells bearing the λ light chain

Enhancing B-Cell Malignancies—On Repurposing Enhancer Activity towards Cancer

Contact Info

Product

Resources

About