Barbro Ehlin-Henriksson Project

We are currently investigating the chemokine receptor expression and ligand induced migration in EBV infected B cells in relation to the expression of the virally encoded proteins.

Barbro Ehlin Henriksson

Barbro Ehlin-Henriksson: I have worked as a technician in the group since 1976 and 2003 I defended my Licentiate thesis. My work has been focused on the establishment of Epstein-Barr virus latency and characterization of the EBV-associated tumor Burkitts lymphoma (BL)(paper 1, 2 and 4). EBV carrying BLs may arise during a germinal center reaction when activated naive B cells differentiate via the germinal center reaction to memory or plasma cells. The differentiation involves somatic mutations and switch of the heavy immunoglobulin chain from IgM to IgG or IgA or IgE. We have earlier shown that EBV genomes are enriched in the peripheral IgA-positive B lymphocytes of healthy carriers (paper 34). This finding raised the question whether memory cells are equally susceptible to EBV as naive cells. We have shown that the relative frequencies of IgM-, IgG- and IgA-positive tonsillar B cells containing EBNA5 were similar to those of the starting population (paper 37). This suggests that in vitro IgM-, IgG-, and IgA-positive cells are equally susceptible if they reside or move near the site for virus production.

Still we do not fully understand how the latency is established and how it is controlled, which cells get infected and how the antibody production is maintained.

One hypothesis concerning the establishment of latent EBV persistence postulates that the infected B cell follows the pathway of antigen-induced B cell activation but without any need for T cell help. The virus obviates that need through its protein products that can provide functionally corresponding signals. LMP2A would substitute for BCR triggered and LMP1 for CD40 triggered signals (Thorley-Lawson, Nat Rev Immunol 2003; 1:75-82).

Very little is known about the initial changes induced by the virus in chemokine receptor expression and chemokine-induced migration. We have shown that the CXCL12 induced migration is reduced already two days after EBV-infection of B cells in vitro (paper 40). The expression of the receptor for CXCL12, CXCR4, is downregulated after one week. This may reflect the in vivo strategy of the virus whereby it avoids retention in the lymphoepithelium where CXCL12 is produced. The infected B cell is permitted to migrate to the interfollicular areas of the tonsil where most EBV-positive cells are found in infectious mononucleosis (IM) patients. This migration may be stimulated by CCL19, produced by dendritic cells, via CCR7 expressed on the infected B cells.

We are currently investigating the chemokine receptor expression and ligand induced migration in EBV infected B cells in relation to the expression of the virally encoded proteins.

Publications

EBV counteracts IL-21-induced apoptosis in an EBV-positive diffuse large B-cell lymphoma cell line.
Wu L, Ehlin-Henriksson B, Zhu H, Ernberg I, Klein G
Int. J. Cancer 2013 Aug;133(3):766-70

Epstein-Barr virus (EBV) provides survival factors to EBV+ diffuse large B-cell lymphoma (DLBCL) lines and modulates cytokine induced specific chemotaxis in EBV+  DLBCL.
Wu L, Ehlin-Henriksson B, Zhou X, Zhu H, Ernberg I, Kis LL, et al
Immunology 2017 12;152(4):562-573

Expression of the chemokine receptors CCR1 and CCR2B is up-regulated in peripheral blood B cells upon EBV infection and in established lymphoblastoid cell lines.
Kholodnyuk I, Rudevica Z, Leonciks A, Ehlin-Henriksson B, Kashuba E
Virology 2017 12;512():1-7

Changes in chemokines and chemokine receptor expression on tonsillar B cells upon Epstein-Barr virus infection.
Ehlin-Henriksson B, Liang W, Cagigi A, Mowafi F, Klein G, Nilsson A
Immunology 2009 Aug;127(4):549-57

Epstein-Barr virus infection negatively impacts the CXCR4-dependent migration of tonsillar B cells.
Ehlin-Henriksson B, Mowafi F, Klein G, Nilsson A
Immunology 2006 Mar;117(3):379-85

Epstein-Barr virus infection negatively impacts the CXCR4-dependent migration of tonsillar B cells.
Ehlin-Henriksson B, Mowafi F, Klein G, Nilsson A
Immunology 2006 Mar;117(3):379-85

EBV-encoded EBNA-5 associates with P14ARF in extranucleolar inclusions and prolongs the survival of P14ARF-expressing cells.
Kashuba E, Mattsson K, Pokrovskaja K, Kiss C, Protopopova M, Ehlin-Henriksson B, et al
Int. J. Cancer 2003 Jul;105(5):644-53

EBV latency: Establishment and Maintenance.
Licentiatavhandling, (2003).

B-lymphocyte subpopulations are equally susceptible to Epstein-Barr virus infection, irrespective of immunoglobulin isotype expression.
Ehlin-Henriksson B, Gordon J, Klein G
Immunology 2003 Apr;108(4):427-30

CD40 ligation downregulates EBNA-2 and LMP-1 expression in EBV-transformed lymphoblastoid cell lines.
Pokrovskaja K, Ehlin-Henriksson B, Kiss C, Challa A, Gordon J, Gogolak P, et al
Int. J. Cancer 2002 Jun;99(5):705-12

EBNA promoter usage in EBV-negative Burkitt lymphoma cell lines converted with a neomycin-resistant EBV strain.
Maeda A, Kiss C, Chen F, Ehlin-Henriksson B, Nagy N, Szekely L, et al
Int. J. Cancer 2001 Sep;93(5):714-9

Epstein-Barr virus genomes are found predominantly in IgA-positive B cells in the blood of healthy carriers.
Ehlin-Henriksson B, Zou JZ, Klein G, Ernberg I
Int. J. Cancer 1999 Sep;83(1):50-4

Restricted expression of Epstein-Barr virus (EBV)-encoded, growth transformation-associated antigens in an EBV- and human herpesvirus type 8-carrying body cavity lymphoma line.
Szekely L, Chen F, Teramoto N, Ehlin-Henriksson B, Pokrovskaja K, Szeles A, et al
J. Gen. Virol. 1998 Jun;79 ( Pt 6)():1445-52

Scavenger receptors mediate adhesion of activated B lymphocytes.
Yokota T, Ehlin-Henriksson B, Hansson GK
Exp. Cell Res. 1998 Feb;239(1):16-22

Phenotype-related differences in the expression of D-type cyclins in human B cell-derived lines.
Pokrovskaja K, Ehlin-Henriksson B, Bartkova J, Bartek J, Scuderi R, Szekely L, et al
Cell Growth Differ. 1996 Dec;7(12):1723-32

Burkitt's lymphoma is a malignancy of mature B cells expressing somatically mutated V region genes.
Klein U, Klein G, Ehlin-Henriksson B, Rajewsky K, Küppers R
Mol. Med. 1995 Jul;1(5):495-505

Publications 1983-1991

Publications 1983-1991 (pdf file) (Pdf file, 65 Kb)

Proceedings

Proceedings (pdf file) (Pdf file, 37 Kb)

Contact

C1 Department of Microbiology, Tumor and Cell Biology