CD20 is dispensable for B-cell receptor signaling but is
required for proper actin polymerization, adhesion and
migration of malignant B cells

J 2020

CD20 is dispensable for B-cell receptor signaling but is required for proper actin polymerization, adhesion and migration of malignant B cells

KOZLOVÁ, Veronika; Aneta LEDEREROVÁ; Adriana LADUNGOVÁ; Helena PESCHELOVÁ; Pavlína JANOVSKÁ et. al.

Basic information

Original name

CD20 is dispensable for B-cell receptor signaling but is required for proper actin polymerization, adhesion and migration of malignant B cells

Authors

Edition

Plos one, San Francisco, Public Library Science, 2020, 1932-6203

Other information

Language

English

Type of outcome

Article in a journal

Field of Study

30204 Oncology

Country of publisher

United States of America

Confidentiality degree

is not subject to a state or trade secret

References:

URL

Impact factor

Impact factor: 3.240

RIV identification code

RIV/00216224:14740/20:00118603

Organization unit

Central European Institute of Technology

DOI

https://doi.org/10.1371/journal.pone.0229170

UT WoS

000535307600007

EID Scopus

2-s2.0-85082310090

Keywords in English

MONOCLONAL-ANTIBODY; ACTIVATION; EXPRESSION; PYK2; LYMPHOMA; MOLECULE; CHANNEL; ANTIGEN

Abstract

In the original language

Surface protein CD20 serves as the critical target of immunotherapy in various B-cell malignancies for decades, however its biological function and regulation remain largely elusive. Better understanding of CD20 function may help to design improved rational therapies to prevent development of resistance. Using CRISPR/Cas9 technique, we have abrogated CD20 expression in five different malignant B-cell lines. We show that CD20 deletion has no effect upon B-cell receptor signaling or calcium flux. Also B-cell survival and proliferation is unaffected in the absence of CD20. On the contrary, we found a strong defect in actin cytoskeleton polymerization and, consequently, defective cell adhesion and migration in response to homeostatic chemokines SDF1 alpha, CCL19 and CCL21. Mechanistically, we could identify a reduction in chemokine-triggered PYK2 activation, a calcium-activated signaling protein involved in activation of MAP kinases and cytoskeleton regulation. These cellular defects in consequence result in a severely disturbed homing of B cells in vivo.

Links

NV15-33561A, research and development project

Name: Rezistence na léčbu monoklonálními protilátkami u B-CLL a B-lymfomů: příčiny vzniku a potenciální intervenční strategie

Cite

KOZLOVÁ, Veronika; Aneta LEDEREROVÁ; Adriana LADUNGOVÁ; Helena PESCHELOVÁ; Pavlína JANOVSKÁ; A. SLUSARCZYK; J. DOMAGALA; Pavel KOPČIL; Viera VAKULOVÁ; Jan OPPELT; Vítězslav BRYJA; Michael DOUBEK; Jiří MAYER; Šárka POSPÍŠILOVÁ and Michal ŠMÍDA. CD20 is dispensable for B-cell receptor signaling but is required for proper actin polymerization, adhesion and migration of malignant B cells. Plos one. San Francisco: Public Library Science, 2020, vol. 15, No 3, p. 0229170-229189. ISSN 1932-6203. Available from: https://doi.org/10.1371/journal.pone.0229170.

@article{1662456,
   author = {Kozlová, Veronika and Ledererová, Aneta and Ladungová, Adriana and Peschelová, Helena and Janovská, Pavlína and Slusarczyk, A. and Domagala, J. and Kopčil, Pavel and Vakulová, Viera and Oppelt, Jan and Bryja, Vítězslav and Doubek, Michael and Mayer, Jiří and Pospíšilová, Šárka and Šmída, Michal},
   article_location = {San Francisco},
   article_number = {3},
   doi = {https://doi.org/10.1371/journal.pone.0229170},
   keywords = {MONOCLONAL-ANTIBODY; ACTIVATION; EXPRESSION; PYK2; LYMPHOMA; MOLECULE; CHANNEL; ANTIGEN},
   language = {eng},
   issn = {1932-6203},
   journal = {Plos one},
   title = {CD20 is dispensable for B-cell receptor signaling but is required for proper actin polymerization, adhesion and migration of malignant B cells},
   url = {https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0229170},
   volume = {15},
   year = {2020}
}

TY  - JOUR
ID  - 1662456
AU  - Kozlová, Veronika - Ledererová, Aneta - Ladungová, Adriana - Peschelová, Helena - Janovská, Pavlína - Slusarczyk, A. - Domagala, J. - Kopčil, Pavel - Vakulová, Viera - Oppelt, Jan - Bryja, Vítězslav - Doubek, Michael - Mayer, Jiří - Pospíšilová, Šárka - Šmída, Michal
PY  - 2020
TI  - CD20 is dispensable for B-cell receptor signaling but is required for proper actin polymerization, adhesion and migration of malignant B cells
JF  - Plos one
VL  - 15
IS  - 3
SP  - 0229170
EP  - 0229170
PB  - Public Library Science
SN  - 19326203
KW  - MONOCLONAL-ANTIBODY
KW  - ACTIVATION
KW  - EXPRESSION
KW  - PYK2
KW  - LYMPHOMA
KW  - MOLECULE
KW  - CHANNEL
KW  - ANTIGEN
UR  - https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0229170
L2  - https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0229170
N2  - Surface protein CD20 serves as the critical target of immunotherapy in various B-cell malignancies for decades, however its biological function and regulation remain largely elusive. Better understanding of CD20 function may help to design improved rational therapies to prevent development of resistance. Using CRISPR/Cas9 technique, we have abrogated CD20 expression in five different malignant B-cell lines. We show that CD20 deletion has no effect upon B-cell receptor signaling or calcium flux. Also B-cell survival and proliferation is unaffected in the absence of CD20. On the contrary, we found a strong defect in actin cytoskeleton polymerization and, consequently, defective cell adhesion and migration in response to homeostatic chemokines SDF1 alpha, CCL19 and CCL21. Mechanistically, we could identify a reduction in chemokine-triggered PYK2 activation, a calcium-activated signaling protein involved in activation of MAP kinases and cytoskeleton regulation. These cellular defects in consequence result in a severely disturbed homing of B cells in vivo.
ER  -

KOZLOVÁ, Veronika; Aneta LEDEREROVÁ; Adriana LADUNGOVÁ; Helena PESCHELOVÁ; Pavlína JANOVSKÁ; A. SLUSARCZYK; J. DOMAGALA; Pavel KOPČIL; Viera VAKULOVÁ; Jan OPPELT; Vítězslav BRYJA; Michael DOUBEK; Jiří MAYER; Šárka POSPÍŠILOVÁ and Michal ŠMÍDA. CD20 is dispensable for B-cell receptor signaling but is required for proper actin polymerization, adhesion and migration of malignant B cells. \textit{Plos one}. San Francisco: Public Library Science, 2020, vol.~15, No~3, p.~0229170-229189. ISSN~1932-6203. Available from: https://doi.org/10.1371/journal.pone.0229170.

Přehled o publikaci