Kidins220 regulates the development of B cells bearing the λ light chain
© 2024, Schaffer et al..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:13 |
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| Enthalten in: |
eLife - 13(2024) vom: 25. Jan. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Schaffer, Anna-Maria [VerfasserIn] |
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| Links: |
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| Themen: |
Adaptive immunity |
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| Anmerkungen: |
Date Completed 29.01.2024 Date Revised 29.01.2024 published: Electronic Citation Status MEDLINE |
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| doi: |
10.7554/eLife.83943 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a adaptive immunity | |
| 650 | 4 | |a immunology | |
| 650 | 4 | |a inflammation | |
| 650 | 4 | |a lambda light chain | |
| 650 | 4 | |a mouse | |
| 650 | 4 | |a recombination | |
| 650 | 4 | |a signalling | |
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| 700 | 1 | |a Hils, Miriam |e verfasserin |4 aut | |
| 700 | 1 | |a Natali, Eriberto |e verfasserin |4 aut | |
| 700 | 1 | |a Babrak, Lmar |e verfasserin |4 aut | |
| 700 | 1 | |a Herr, Laurenz Alexander |e verfasserin |4 aut | |
| 700 | 1 | |a Romero-Mulero, Mari Carmen |e verfasserin |4 aut | |
| 700 | 1 | |a Cabezas-Wallscheid, Nina |e verfasserin |4 aut | |
| 700 | 1 | |a Rizzi, Marta |e verfasserin |4 aut | |
| 700 | 1 | |a Miho, Enkelejda |e verfasserin |4 aut | |
| 700 | 1 | |a Schamel, Wolfgang W A |e verfasserin |4 aut | |
| 700 | 1 | |a Minguet, Susana |e verfasserin |4 aut | |
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