Lymphoblastoid cell line with B1 cell characteristics established from a chronic lymphocytic leukemia clone by in vitro EBV infection

Anders Rosén, Ann Charlotte Bergh, P. Gogolák, Chamilly Evaldsson, Anna Lanemo Myhrinder, Eva Hellqvist, Abu Rasul, Magnus Björkholm, Mattias Jansson, Larry Mansouri, Anquan Liu, Bin Tean Teh, Richard Rosenquist, Eva Klein

Research output: Article

29 Citations (Scopus)

Abstract

Chronic lymphocytic leukemia (CLL) cells express the receptor for Epstein-Barr virus (EBV) and can be infected in vitro. Infected cells do not express the growth-promoting set of EBV-encoded genes and therefore they do not yield LCLs, in most experiments. With exceptional clones, lines were obtained however. We describe a new line, HG3, established by in vitro EBV-infection from an IGHV1-2 unmutated CLL patient clone. All cells expressed EBNA-2 and LMP-1, the EBV-encoded genes pivotal for transformation. The karyotype, FISH cytogenetics and SNP-array profile of the line and the patient's ex vivo clone showed biallelic 13q14 deletions with genomic loss of DLEU7, miR15a/miR16-1, the two micro-RNAs that are deleted in 50% of CLL cases. Further features of CLL cells were: expression of CD5/CD20/CD27/CD43 and release of IgM natural antibodies reacting with oxLDL-like epitopes on apoptotic cells (cf. stereotyped subset-1). Comparison with two LCLs established from normal B cells showed 32 genes expressed at higher levels (.> 2-fold). Among these were LHX2 and LILRA. These genes may play a role in the development of the disease. LHX2 expression was shown in self-renewing multipotent hematopoietic stem cells, and LILRA4 codes for a receptor for bone marrow stromal cell antigen-2 that contributes to B cell development. Twenty-four genes were expressed at lower levels, among these PARD3 that is essential for asymmetric cell division. These genes may contribute to establish precursors of CLL clones by regulation of cellular phenotype in the hematopoietic compartment. Expression of CD5/CD20/CD27/CD43 and spontaneous production of natural antibodies may identify the CLL cell as a self-renewing B1 lymphocyte.

Original languageEnglish
Pages (from-to)18-27
Number of pages10
JournalOncoImmunology
Volume1
Issue number1
DOIs
Publication statusPublished - 2012

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Epstein-Barr Virus Infections
B-Cell Chronic Lymphocytic Leukemia
Clone Cells
Cell Line
Genes
Human Herpesvirus 4
B-Lymphocytes
Complement 3d Receptors
Asymmetric Cell Division
Multipotent Stem Cells
Hematopoietic Stem Cells
MicroRNAs
Mesenchymal Stromal Cells
Karyotype
Cytogenetics
Antibody Formation
Single Nucleotide Polymorphism
Immunoglobulin M
In Vitro Techniques
Epitopes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Oncology
  • Immunology

Cite this

Lymphoblastoid cell line with B1 cell characteristics established from a chronic lymphocytic leukemia clone by in vitro EBV infection. / Rosén, Anders; Bergh, Ann Charlotte; Gogolák, P.; Evaldsson, Chamilly; Myhrinder, Anna Lanemo; Hellqvist, Eva; Rasul, Abu; Björkholm, Magnus; Jansson, Mattias; Mansouri, Larry; Liu, Anquan; Teh, Bin Tean; Rosenquist, Richard; Klein, Eva.

In: OncoImmunology, Vol. 1, No. 1, 2012, p. 18-27.

Research output: Article

Rosén, A, Bergh, AC, Gogolák, P, Evaldsson, C, Myhrinder, AL, Hellqvist, E, Rasul, A, Björkholm, M, Jansson, M, Mansouri, L, Liu, A, Teh, BT, Rosenquist, R & Klein, E 2012, 'Lymphoblastoid cell line with B1 cell characteristics established from a chronic lymphocytic leukemia clone by in vitro EBV infection', OncoImmunology, vol. 1, no. 1, pp. 18-27. https://doi.org/10.4161/onci.1.1.18400
Rosén, Anders ; Bergh, Ann Charlotte ; Gogolák, P. ; Evaldsson, Chamilly ; Myhrinder, Anna Lanemo ; Hellqvist, Eva ; Rasul, Abu ; Björkholm, Magnus ; Jansson, Mattias ; Mansouri, Larry ; Liu, Anquan ; Teh, Bin Tean ; Rosenquist, Richard ; Klein, Eva. / Lymphoblastoid cell line with B1 cell characteristics established from a chronic lymphocytic leukemia clone by in vitro EBV infection. In: OncoImmunology. 2012 ; Vol. 1, No. 1. pp. 18-27.
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T1 - Lymphoblastoid cell line with B1 cell characteristics established from a chronic lymphocytic leukemia clone by in vitro EBV infection

AU - Rosén, Anders

AU - Bergh, Ann Charlotte

AU - Gogolák, P.

AU - Evaldsson, Chamilly

AU - Myhrinder, Anna Lanemo

AU - Hellqvist, Eva

AU - Rasul, Abu

AU - Björkholm, Magnus

AU - Jansson, Mattias

AU - Mansouri, Larry

AU - Liu, Anquan

AU - Teh, Bin Tean

AU - Rosenquist, Richard

AU - Klein, Eva

PY - 2012

Y1 - 2012

N2 - Chronic lymphocytic leukemia (CLL) cells express the receptor for Epstein-Barr virus (EBV) and can be infected in vitro. Infected cells do not express the growth-promoting set of EBV-encoded genes and therefore they do not yield LCLs, in most experiments. With exceptional clones, lines were obtained however. We describe a new line, HG3, established by in vitro EBV-infection from an IGHV1-2 unmutated CLL patient clone. All cells expressed EBNA-2 and LMP-1, the EBV-encoded genes pivotal for transformation. The karyotype, FISH cytogenetics and SNP-array profile of the line and the patient's ex vivo clone showed biallelic 13q14 deletions with genomic loss of DLEU7, miR15a/miR16-1, the two micro-RNAs that are deleted in 50% of CLL cases. Further features of CLL cells were: expression of CD5/CD20/CD27/CD43 and release of IgM natural antibodies reacting with oxLDL-like epitopes on apoptotic cells (cf. stereotyped subset-1). Comparison with two LCLs established from normal B cells showed 32 genes expressed at higher levels (.> 2-fold). Among these were LHX2 and LILRA. These genes may play a role in the development of the disease. LHX2 expression was shown in self-renewing multipotent hematopoietic stem cells, and LILRA4 codes for a receptor for bone marrow stromal cell antigen-2 that contributes to B cell development. Twenty-four genes were expressed at lower levels, among these PARD3 that is essential for asymmetric cell division. These genes may contribute to establish precursors of CLL clones by regulation of cellular phenotype in the hematopoietic compartment. Expression of CD5/CD20/CD27/CD43 and spontaneous production of natural antibodies may identify the CLL cell as a self-renewing B1 lymphocyte.

AB - Chronic lymphocytic leukemia (CLL) cells express the receptor for Epstein-Barr virus (EBV) and can be infected in vitro. Infected cells do not express the growth-promoting set of EBV-encoded genes and therefore they do not yield LCLs, in most experiments. With exceptional clones, lines were obtained however. We describe a new line, HG3, established by in vitro EBV-infection from an IGHV1-2 unmutated CLL patient clone. All cells expressed EBNA-2 and LMP-1, the EBV-encoded genes pivotal for transformation. The karyotype, FISH cytogenetics and SNP-array profile of the line and the patient's ex vivo clone showed biallelic 13q14 deletions with genomic loss of DLEU7, miR15a/miR16-1, the two micro-RNAs that are deleted in 50% of CLL cases. Further features of CLL cells were: expression of CD5/CD20/CD27/CD43 and release of IgM natural antibodies reacting with oxLDL-like epitopes on apoptotic cells (cf. stereotyped subset-1). Comparison with two LCLs established from normal B cells showed 32 genes expressed at higher levels (.> 2-fold). Among these were LHX2 and LILRA. These genes may play a role in the development of the disease. LHX2 expression was shown in self-renewing multipotent hematopoietic stem cells, and LILRA4 codes for a receptor for bone marrow stromal cell antigen-2 that contributes to B cell development. Twenty-four genes were expressed at lower levels, among these PARD3 that is essential for asymmetric cell division. These genes may contribute to establish precursors of CLL clones by regulation of cellular phenotype in the hematopoietic compartment. Expression of CD5/CD20/CD27/CD43 and spontaneous production of natural antibodies may identify the CLL cell as a self-renewing B1 lymphocyte.

KW - Cell-of-origin

KW - Chronic lymphocytic leukemia

KW - Human b1 cells

KW - Leukemogenesis

KW - Lymphoblastoid cell line

KW - Self-renewing hematopoietic stem cells

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