Molecular Signals Involved in Human B Cell Migration into the Retina: In Vitro Investigation of ICAM-1, VCAM-1, and CXCL13

ABSTRACT

Purpose: B cells participate in diverse retinal immunopathologies. Endothelial adhesion molecules and chemokines direct leukocyte trafficking. We examined the involvement of three molecular signals in retinal transendothelial migration of human B cells: ICAM-1, VCAM-1, and CXCL13.

Methods: Peripheral blood B cells were isolated by negative selection. Migration was studied in transwells populated with human retinal endothelial monolayers, using antibody to block ICAM-1 or VCAM-1. Retinal expression of CXCL13 was investigated.

Results: B cells crossed retinal endothelium. ICAM-1 blockade significantly reduced migration when results for all subjects were combined, and for a majority when results were analyzed by individual. This effect was irrespective of the presence or absence of CXCL13, although CXCL13 increased migration. CXCL13 was detected in neural retina and retinal pigment epithelium. Endothelial cells of some retinal vessels presented CXCL13 protein.

Conclusion: ICAM-1 blockade may be an effective treatment in some patients with retinal diseases that involve B cells.

Keywords:

• B cell
• CXCL
• human
• ICAM-1
• retina13

ACKNOWLEDGMENTS

Author contributions: JRS, BA, ASB and AJS designed the study; ASB, AJS, AO, SEF, LMA, YM, and SL performed the experiments; ASB, AJS and JRS wrote the article, with input from AO, SEF, LMA, YM, SL, and BA. The authors wish to thank Denise A. Galloway, PhD (Fred Hutchinson Cancer Institute, Seattle, WA), for gifting the LXSN16E6E7 viral construct, and Keryn A. Williams, PhD (Flinders University, Adelaide, Australia) for critical review of the manuscript.

DECLARATION OF INTEREST

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

FUNDING

This work was supported by grants from the National Eye Institute/National Institutes of Health (R21 EY022009) and the Australian Research Council (FT130101648).

Additional information

Funding

This work was supported by grants from the National Eye Institute/National Institutes of Health (R21 EY022009) and the Australian Research Council (FT130101648).