Expression of chemokine receptors, CXCR4 and CXCR5, and chemokines, BLC and SDF-1, in the eyes of patients with primary intraocular lymphoma.
OBJECTIVE
Chemokines have a range of biologic activities, including regulation of leukocyte trafficking, modulation of hematopoietic cell proliferation, and adhesion to extracellular matrix molecules. Specifically, B-lymphocyte chemoattractant (BLC); BCA-1; CXCL13, SCYB13) and stromal cell-derived factor-1 (SDF-1, CXCL12, SCYB12) are chemotactic for human B cells, and their ligands CXCR4 and CXCR5 are differentially expressed on B cells, including malignant B cells. We investigated the expression of these chemokine/chemokine receptors in eyes with primary intraocular B-cell lymphoma (PIOL).


METHODS
Observational case series (human tissue study).


METHODS
Three freshly enucleated eyes with PIOL and a normal autopsied eye were frozen and sectioned. The sections were evaluated using immunohistochemistry (avidin-biotin-complex immunoperoxidase technique) for CXCR4, CXCR5, BLC, and SDF-1 to detect the expression and location. Reverse transcriptase-polymerase chain reaction was used to detect chemokine transcripts of CXCR4, CXCR5, BLC, and SDF-1 in PIOL and retinal pigment epithelium (RPE) cells after microdissection-either by laser capture (Arcturus) or by manual dissection-from frozen sections.


RESULTS
The three PIOL eyes showed similar pathology, with typical diffuse large B-lymphoma cells subjacent to the RPE. The eyes also demonstrated a similar chemokine profile. High expression levels of CXCR4 and CXCR5 were found limited to the lymphoma cells. In contrast, BLC protein was expressed in the RPE but not located in other ocular resident cells. SDF-1 was barely detected in a few RPE cells. CXCR4 and CXCR5 transcripts were detected abundantly in lymphoma cells, whereas BLC and SDF-1 transcripts were detected only in the RPE and not the malignant cells. No chemokine expression was detected on the RPE cells in the normal control eye.


CONCLUSIONS
Chemokines and chemokine receptors selective for B cells were identified in RPE and malignant B cells, respectively. BLC, and possibly SDF-1, attracts both normal and malignant B-cells while promoting migration of only small numbers of T cells and macrophages. We propose that B-cell chemokines may be involved in the pathogenesis of PIOL by selectively attracting lymphoma cells to the RPE from the choroidal circulation. Our data suggest that inhibition of B-cell chemoattractants could be a future strategy for the treatment of PIOL.
Chan
Chi-Chao
CC
Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bldg. 10, Rm. 10N103, 90 Center Drive, Bethesda, MD 20892-1857, USA.
Shen
DeFen
D
Hackett
Joseph J
JJ
Buggage
Ronald R
RR
Tuaillon
Nadine
N
D001402:B-Lymphocytes / Q000378:metabolism; D054377:Chemokine CXCL12; D054382:Chemokine CXCL13; D019743:Chemokines, CXC / Q000235:genetics / Q000378:metabolism*; D015353:Eye Enucleation; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D016393:Lymphoma, B-Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism; D010857:Pigment Epithelium of Eye / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D054380:Receptors, CXCR5; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine / Q000235:genetics / Q000378:metabolism*; D019572:Retinal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction
C515255:CXCL12 protein, human; C110663:CXCL13 protein, human; C095085:CXCR5 protein, human; D054377:Chemokine CXCL12; D054382:Chemokine CXCL13; D019743:Chemokines, CXC; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D054380:Receptors, CXCR5; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine