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SLAMF receptors negatively regulate B cell receptor signaling in chronic lymphocytic leukemia via recruitment of prohibitin-2

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SLAMF receptors negatively regulate B cell receptor signaling in chronic lymphocytic leukemia via recruitment of prohibitin-2. / von Wenserski, Lisa; Schultheiß, Christoph; Bolz, Sarah; Schliffke, Simon; Simnica, Donjete; Willscher, Edith; Gerull, Helwe; Wolters-Eisfeld, Gerrit; Riecken, Kristoffer; Fehse, Boris; Altfeld, Marcus; Nollau, Peter; Binder, Mascha.

In: LEUKEMIA, Vol. 35, No. 4, 04.2021, p. 1073-1086.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

von Wenserski, L, Schultheiß, C, Bolz, S, Schliffke, S, Simnica, D, Willscher, E, Gerull, H, Wolters-Eisfeld, G, Riecken, K, Fehse, B, Altfeld, M, Nollau, P & Binder, M 2021, 'SLAMF receptors negatively regulate B cell receptor signaling in chronic lymphocytic leukemia via recruitment of prohibitin-2', LEUKEMIA, vol. 35, no. 4, pp. 1073-1086. https://doi.org/10.1038/s41375-020-01025-z

APA

von Wenserski, L., Schultheiß, C., Bolz, S., Schliffke, S., Simnica, D., Willscher, E., Gerull, H., Wolters-Eisfeld, G., Riecken, K., Fehse, B., Altfeld, M., Nollau, P., & Binder, M. (2021). SLAMF receptors negatively regulate B cell receptor signaling in chronic lymphocytic leukemia via recruitment of prohibitin-2. LEUKEMIA, 35(4), 1073-1086. https://doi.org/10.1038/s41375-020-01025-z

Vancouver

von Wenserski L, Schultheiß C, Bolz S, Schliffke S, Simnica D, Willscher E et al. SLAMF receptors negatively regulate B cell receptor signaling in chronic lymphocytic leukemia via recruitment of prohibitin-2. LEUKEMIA. 2021 Apr;35(4):1073-1086. https://doi.org/10.1038/s41375-020-01025-z

Bibtex

@article{cc3f3f602ed948b48aba54d9ebf79988,
title = "SLAMF receptors negatively regulate B cell receptor signaling in chronic lymphocytic leukemia via recruitment of prohibitin-2",
abstract = "We identified a subset of Chronic Lymphocytic Leukemia (CLL) patients with high Signaling Lymphocytic Activation Molecule Family (SLAMF) receptor-related signaling that showed an indolent clinical course. Since SLAMF receptors play a role in NK cell biology, we reasoned that these receptors may impact NK cell-mediated CLL immunity. Indeed, our experiments showed significantly decreased degranulation capacity of primary NK cells from CLL patients expressing low levels of SLAMF1 and SLAMF7. Since the SLAMFlow signature was strongly associated with an unmutated CLL immunoglobulin heavy chain (IGHV) status in large datasets, we investigated the impact of SLAMF1 and SLAMF7 on the B cell receptor (BCR) signaling axis. Overexpression of SLAMF1 or SLAMF7 in IGHV mutated CLL cell models resulted in reduced proliferation and impaired responses to BCR ligation, whereas the knockout of both receptors showed opposing effects and increased sensitivity toward inhibition of components of the BCR pathway. Detailed molecular analyzes showed that SLAMF1 and SLAMF7 receptors mediate their BCR pathway antagonistic effects via recruitment of prohibitin-2 (PHB2) thereby impairing its role in signal transduction downstream the IGHV-mutant IgM-BCR. Together, our data indicate that SLAMF receptors are important modulators of the BCR signaling axis and may improve immune control in CLL by interference with NK cells.",
author = "{von Wenserski}, Lisa and Christoph Schulthei{\ss} and Sarah Bolz and Simon Schliffke and Donjete Simnica and Edith Willscher and Helwe Gerull and Gerrit Wolters-Eisfeld and Kristoffer Riecken and Boris Fehse and Marcus Altfeld and Peter Nollau and Mascha Binder",
year = "2021",
month = apr,
doi = "10.1038/s41375-020-01025-z",
language = "English",
volume = "35",
pages = "1073--1086",
journal = "LEUKEMIA",
issn = "0887-6924",
publisher = "NATURE PUBLISHING GROUP",
number = "4",

}

RIS

TY - JOUR

T1 - SLAMF receptors negatively regulate B cell receptor signaling in chronic lymphocytic leukemia via recruitment of prohibitin-2

AU - von Wenserski, Lisa

AU - Schultheiß, Christoph

AU - Bolz, Sarah

AU - Schliffke, Simon

AU - Simnica, Donjete

AU - Willscher, Edith

AU - Gerull, Helwe

AU - Wolters-Eisfeld, Gerrit

AU - Riecken, Kristoffer

AU - Fehse, Boris

AU - Altfeld, Marcus

AU - Nollau, Peter

AU - Binder, Mascha

PY - 2021/4

Y1 - 2021/4

N2 - We identified a subset of Chronic Lymphocytic Leukemia (CLL) patients with high Signaling Lymphocytic Activation Molecule Family (SLAMF) receptor-related signaling that showed an indolent clinical course. Since SLAMF receptors play a role in NK cell biology, we reasoned that these receptors may impact NK cell-mediated CLL immunity. Indeed, our experiments showed significantly decreased degranulation capacity of primary NK cells from CLL patients expressing low levels of SLAMF1 and SLAMF7. Since the SLAMFlow signature was strongly associated with an unmutated CLL immunoglobulin heavy chain (IGHV) status in large datasets, we investigated the impact of SLAMF1 and SLAMF7 on the B cell receptor (BCR) signaling axis. Overexpression of SLAMF1 or SLAMF7 in IGHV mutated CLL cell models resulted in reduced proliferation and impaired responses to BCR ligation, whereas the knockout of both receptors showed opposing effects and increased sensitivity toward inhibition of components of the BCR pathway. Detailed molecular analyzes showed that SLAMF1 and SLAMF7 receptors mediate their BCR pathway antagonistic effects via recruitment of prohibitin-2 (PHB2) thereby impairing its role in signal transduction downstream the IGHV-mutant IgM-BCR. Together, our data indicate that SLAMF receptors are important modulators of the BCR signaling axis and may improve immune control in CLL by interference with NK cells.

AB - We identified a subset of Chronic Lymphocytic Leukemia (CLL) patients with high Signaling Lymphocytic Activation Molecule Family (SLAMF) receptor-related signaling that showed an indolent clinical course. Since SLAMF receptors play a role in NK cell biology, we reasoned that these receptors may impact NK cell-mediated CLL immunity. Indeed, our experiments showed significantly decreased degranulation capacity of primary NK cells from CLL patients expressing low levels of SLAMF1 and SLAMF7. Since the SLAMFlow signature was strongly associated with an unmutated CLL immunoglobulin heavy chain (IGHV) status in large datasets, we investigated the impact of SLAMF1 and SLAMF7 on the B cell receptor (BCR) signaling axis. Overexpression of SLAMF1 or SLAMF7 in IGHV mutated CLL cell models resulted in reduced proliferation and impaired responses to BCR ligation, whereas the knockout of both receptors showed opposing effects and increased sensitivity toward inhibition of components of the BCR pathway. Detailed molecular analyzes showed that SLAMF1 and SLAMF7 receptors mediate their BCR pathway antagonistic effects via recruitment of prohibitin-2 (PHB2) thereby impairing its role in signal transduction downstream the IGHV-mutant IgM-BCR. Together, our data indicate that SLAMF receptors are important modulators of the BCR signaling axis and may improve immune control in CLL by interference with NK cells.

U2 - 10.1038/s41375-020-01025-z

DO - 10.1038/s41375-020-01025-z

M3 - SCORING: Journal article

C2 - 32826957

VL - 35

SP - 1073

EP - 1086

JO - LEUKEMIA

JF - LEUKEMIA

SN - 0887-6924

IS - 4

ER -