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

Anna-Maria Schaffer; Gina Jasmin Fiala; Miriam Hils; Eriberto Natali; Lmar Babrak; Laurenz Alexander Herr; Mari Carmen Romero-Mulero; Nina Cabezas-Wallscheid; Marta Rizzi; Enkelejda Miho; Wolfgang W A Schamel; Susana Minguet

doi:10.7554/eLife.83943

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

Elife. 2024 Jan 25:13:e83943. doi: 10.7554/eLife.83943.

Authors

Anna-Maria Schaffer^{1

2

3}, Gina Jasmin Fiala^{1

2

3}, Miriam Hils^{1

3

4}, Eriberto Natali⁵, Lmar Babrak⁵, Laurenz Alexander Herr^{1

2

3}, Mari Carmen Romero-Mulero^{1

6}, Nina Cabezas-Wallscheid^{6

7}, Marta Rizzi^{3

7

8

9}, Enkelejda Miho^{5

10

11}, Wolfgang W A Schamel^{1

2

3}, Susana Minguet^{1

2

3}

Affiliations

¹ Faculty of Biology, Albert-Ludwigs-University of Freiburg, Freiburg, Germany.
² Signalling Research Centers BIOSS and CIBSS, University of Freiburg, Freiburg, Germany.
³ Center of Chronic Immunodeficiency CCI, University Clinics and Medical Faculty, Freiburg, Germany.
⁴ Department of Dermatology and Allergy Biederstein, School of Medicine, Technical University of Munich, Munich, Germany.
⁵ Institute of Medical Engineering and Medical Informatics, School of Life Sciences, FHNW 15 University of Applied Sciences and Arts Northwestern Switzerland, Muttenz, Switzerland.
⁶ Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany.
⁷ CIBSS - Centre for Integrative Biological Signalling Studies, University of Freiburg, Freiburg, Germany.
⁸ Division of Clinical and Experimental Immunology, Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
⁹ Department of Rheumatology and Clinical Immunology, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
¹⁰ aiNET GmbH, Basel, Switzerland.
¹¹ SIB Swiss Institute of Bioinformatics, Lausanne, Switzerland.

Abstract

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.

Keywords: B cells; adaptive immunity; immunology; inflammation; lambda light chain; mouse; recombination; signalling.

MeSH terms

B-Lymphocytes* / metabolism
Signal Transduction*

Abstract

MeSH terms

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