Barbro Ehlin-Henriksson Project
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.
Ehlin-Henriksson B, Liang W, Cagigi A, Mowafi F, Klein G, Nilsson A.
Changes in chemokines and chemokine receptor expression on tonsillar B cells upon Epstein-Barr virus infection.
Immunology. 2009 Aug;127(4):549-57.
Link to the abstract in PubMed
Ehlin-Henriksson B., Mowafi F,. Klein G. and Nilsson A
Epstein-Barr Virus infection negatively impacts the CXCR4-dependent migration of tonsillar B cells
Immunology, 117, 379-385 (2006).
Ehlin-Henriksson B., Mowafi F., Klein G., and Nilsson A.
Epstein-Barr virus infection negatively impacts the CXCR4-dependent migration of tonsillar B cells.
Immunology, 117, 379-385, 2006
Kashuba E., Mattsson K., Pokrovskaja K., Protopopova M., Kiss C., Ehlin-Henriksson B., Klein G. And Szekely L.
EBV-encoded EBNA-5 associates with p14ARF in extranucleolar inclusions and prolongs the survival of p14ARF-expressing cells.
Int. J. Cancer, 105, 644-653, (2003).
EBV latency: Establishment and Maintenance.
Ehlin-Henriksson B., Gordon J. And Klein G.
B lymphocyte subpopulations are equally susceptible to Epstein-Barr virus-infection irrespective of immunoglobulin isotype expression
Immunology, 108, 427-430, (2003).
Pokrovskaja K., Ehlin-Henriksson B., Kiss C., Challa A., Gordon J., Goglak P., Teramoto N., Klein and Klein G.
CD40 ligation down regulates EBNA-2 and LMP-1 expression in EBV transformed lymphoblastoid cell lines.
Int. J. Cancer, 99, 705-712, (2002)
Maeda A., Kiss C., Chen Fu, Ehlin-Henriksson B., Nagy N., Szekely L., Takada K., Klein E. And Klein G.
EBNA promoter usage in EBV-negative Burkitt lymphoma cell lines converted with a neomycin-resistant EBV strain
Int. J. Cancer, 93, 714-719, (2001).
Ehlin-Henriksson B., Zou J-Z,. Klein G. and Ernberg I
Epstein-Barr Virus genomes are predominantly found in IgA-positive B-cells in blood of healthy carriers.
Int. J. Cancer, 83, 50-54, (1999).
Szekely L., Chen Fu, Teramoto N., Ehlin-Henriksson B., Pokrovskaja K., Szeles A., Manneborg-Sandlund A., Löwbeer M., Lennette E. T. And Klein G.
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.
J. Gen. Virol. 79, 1445-1452, (1998).
Yokota T., Ehlin-Henriksson B. and Hansson G., K.
Scavenger receptors mediate adhesion of activated B lymphocytes.
Exp. Cell Research, 239, 16-22, (1998).
Pokrovskaja K., Ehlin-Henriksson B., Bartova J., Bartek J., Scuderi R., Szekely L., Wiman K. G., and Klein G
Phenotypic-related differences in the expression of D-type cyclins in human B cell-derived lines.
Cell Growth & Differentiation, 7, 1723-1732, (1996).
Klein U., Klein G., Ehlin-Henriksson B., Rajewsky K., and Kuppers R.
Burkitt´s lymphoma is a malignancy of mature B cells expressing somatically mutated V region genes
Molecular Med., 1, 495-505, (1995)