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Stereotypical chronic lymphocytic leukemia B-cell receptors recognize survival promoting antigens on stromal cells

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Stereotypical chronic lymphocytic leukemia B-cell receptors recognize survival promoting antigens on stromal cells. / Binder, Mascha; Léchenne, Barbara; Ummanni, Ramesh; Scharf, Christan; Balabanov, Stefan; Trusch, Maria; Schlüter, Hartmut; Braren, Ingke; Spillner, Edzard; Trepel, Martin.

in: PLOS ONE, Jahrgang 5, Nr. 12, 30.12.2010, S. e15992.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Binder, M, Léchenne, B, Ummanni, R, Scharf, C, Balabanov, S, Trusch, M, Schlüter, H, Braren, I, Spillner, E & Trepel, M 2010, 'Stereotypical chronic lymphocytic leukemia B-cell receptors recognize survival promoting antigens on stromal cells', PLOS ONE, Jg. 5, Nr. 12, S. e15992. https://doi.org/10.1371/journal.pone.0015992

APA

Binder, M., Léchenne, B., Ummanni, R., Scharf, C., Balabanov, S., Trusch, M., Schlüter, H., Braren, I., Spillner, E., & Trepel, M. (2010). Stereotypical chronic lymphocytic leukemia B-cell receptors recognize survival promoting antigens on stromal cells. PLOS ONE, 5(12), e15992. https://doi.org/10.1371/journal.pone.0015992

Vancouver

Binder M, Léchenne B, Ummanni R, Scharf C, Balabanov S, Trusch M et al. Stereotypical chronic lymphocytic leukemia B-cell receptors recognize survival promoting antigens on stromal cells. PLOS ONE. 2010 Dez 30;5(12):e15992. https://doi.org/10.1371/journal.pone.0015992

Bibtex

@article{3a3977388d7f426290a914f5a6ad3734,
title = "Stereotypical chronic lymphocytic leukemia B-cell receptors recognize survival promoting antigens on stromal cells",
abstract = "Chronic lymphocytic leukemia (CLL) is the most common leukemia in the Western world. Survival of CLL cells depends on their close contact with stromal cells in lymphatic tissues, bone marrow and blood. This microenvironmental regulation of CLL cell survival involves the stromal secretion of chemo- and cytokines as well as the expression of adhesion molecules. Since CLL survival may also be driven by antigenic stimulation through the B-cell antigen receptor (BCR), we explored the hypothesis that these processes may be linked to each other. We tested if stromal cells could serve as an antigen reservoir for CLL cells, thus promoting CLL cell survival by stimulation through the BCR. As a proof of principle, we found that two CLL BCRs with a common stereotyped heavy chain complementarity-determining region 3 (previously characterized as {"}subset 1{"}) recognize antigens highly expressed in stromal cells--vimentin and calreticulin. Both antigens are well-documented targets of autoantibodies in autoimmune disorders. We demonstrated that vimentin is displayed on the surface of viable stromal cells and that it is present and bound by the stereotyped CLL BCR in CLL-stroma co-culture supernatant. Blocking the vimentin antigen by recombinant soluble CLL BCR under CLL-stromal cell co-culture conditions reduces stroma-mediated anti-apoptotic effects by 20-45%. We therefore conclude that CLL BCR stimulation by stroma-derived antigens can contribute to the protective effect that the stroma exerts on CLL cells. This finding sheds a new light on the understanding of the pathobiology of this so far mostly incurable disease.",
keywords = "Antigens, Calreticulin, Complementarity Determining Regions, Electrophoresis, Gel, Two-Dimensional, HeLa Cells, Humans, Immunoglobulin G, Leukemia, Lymphocytic, Chronic, B-Cell, Leukocytes, Mononuclear, Microscopy, Fluorescence, Receptors, Antigen, B-Cell, Recombinant Proteins, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Stromal Cells, Vimentin, Journal Article, Research Support, Non-U.S. Gov't",
author = "Mascha Binder and Barbara L{\'e}chenne and Ramesh Ummanni and Christan Scharf and Stefan Balabanov and Maria Trusch and Hartmut Schl{\"u}ter and Ingke Braren and Edzard Spillner and Martin Trepel",
year = "2010",
month = dec,
day = "30",
doi = "10.1371/journal.pone.0015992",
language = "English",
volume = "5",
pages = "e15992",
journal = "PLOS ONE",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "12",

}

RIS

TY - JOUR

T1 - Stereotypical chronic lymphocytic leukemia B-cell receptors recognize survival promoting antigens on stromal cells

AU - Binder, Mascha

AU - Léchenne, Barbara

AU - Ummanni, Ramesh

AU - Scharf, Christan

AU - Balabanov, Stefan

AU - Trusch, Maria

AU - Schlüter, Hartmut

AU - Braren, Ingke

AU - Spillner, Edzard

AU - Trepel, Martin

PY - 2010/12/30

Y1 - 2010/12/30

N2 - Chronic lymphocytic leukemia (CLL) is the most common leukemia in the Western world. Survival of CLL cells depends on their close contact with stromal cells in lymphatic tissues, bone marrow and blood. This microenvironmental regulation of CLL cell survival involves the stromal secretion of chemo- and cytokines as well as the expression of adhesion molecules. Since CLL survival may also be driven by antigenic stimulation through the B-cell antigen receptor (BCR), we explored the hypothesis that these processes may be linked to each other. We tested if stromal cells could serve as an antigen reservoir for CLL cells, thus promoting CLL cell survival by stimulation through the BCR. As a proof of principle, we found that two CLL BCRs with a common stereotyped heavy chain complementarity-determining region 3 (previously characterized as "subset 1") recognize antigens highly expressed in stromal cells--vimentin and calreticulin. Both antigens are well-documented targets of autoantibodies in autoimmune disorders. We demonstrated that vimentin is displayed on the surface of viable stromal cells and that it is present and bound by the stereotyped CLL BCR in CLL-stroma co-culture supernatant. Blocking the vimentin antigen by recombinant soluble CLL BCR under CLL-stromal cell co-culture conditions reduces stroma-mediated anti-apoptotic effects by 20-45%. We therefore conclude that CLL BCR stimulation by stroma-derived antigens can contribute to the protective effect that the stroma exerts on CLL cells. This finding sheds a new light on the understanding of the pathobiology of this so far mostly incurable disease.

AB - Chronic lymphocytic leukemia (CLL) is the most common leukemia in the Western world. Survival of CLL cells depends on their close contact with stromal cells in lymphatic tissues, bone marrow and blood. This microenvironmental regulation of CLL cell survival involves the stromal secretion of chemo- and cytokines as well as the expression of adhesion molecules. Since CLL survival may also be driven by antigenic stimulation through the B-cell antigen receptor (BCR), we explored the hypothesis that these processes may be linked to each other. We tested if stromal cells could serve as an antigen reservoir for CLL cells, thus promoting CLL cell survival by stimulation through the BCR. As a proof of principle, we found that two CLL BCRs with a common stereotyped heavy chain complementarity-determining region 3 (previously characterized as "subset 1") recognize antigens highly expressed in stromal cells--vimentin and calreticulin. Both antigens are well-documented targets of autoantibodies in autoimmune disorders. We demonstrated that vimentin is displayed on the surface of viable stromal cells and that it is present and bound by the stereotyped CLL BCR in CLL-stroma co-culture supernatant. Blocking the vimentin antigen by recombinant soluble CLL BCR under CLL-stromal cell co-culture conditions reduces stroma-mediated anti-apoptotic effects by 20-45%. We therefore conclude that CLL BCR stimulation by stroma-derived antigens can contribute to the protective effect that the stroma exerts on CLL cells. This finding sheds a new light on the understanding of the pathobiology of this so far mostly incurable disease.

KW - Antigens

KW - Calreticulin

KW - Complementarity Determining Regions

KW - Electrophoresis, Gel, Two-Dimensional

KW - HeLa Cells

KW - Humans

KW - Immunoglobulin G

KW - Leukemia, Lymphocytic, Chronic, B-Cell

KW - Leukocytes, Mononuclear

KW - Microscopy, Fluorescence

KW - Receptors, Antigen, B-Cell

KW - Recombinant Proteins

KW - Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

KW - Stromal Cells

KW - Vimentin

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1371/journal.pone.0015992

DO - 10.1371/journal.pone.0015992

M3 - SCORING: Journal article

C2 - 21209908

VL - 5

SP - e15992

JO - PLOS ONE

JF - PLOS ONE

SN - 1932-6203

IS - 12

ER -