Background/Purpose:

Experimental data suggest that B cells must migrate and accumulate into the synovial membrane to exert their pathogenic role in rheumatoid arthritis (RA). Leukocyte extravasation requires a number of coordinated adhesives events between circulating leukocytes and endothelial cells, a process known as the adhesion cascade. While the molecules involved in the sequential steps of the adhesion cascade for neutrophils and T lymphocytes have been well established, little is known about this process in B cells. 

Objective: To determine the adhesion molecules involved in the interactions between B cells and endothelium under dynamic condition resembling those of postcapillary venules during the inflammatory response. 

Methods:

The surface expression levels of very late antigen (VLA)-4, intercellular adhesion molecule (ICAM)-1 and L-selectin were assessed by double-colour staining flow cytometry analysis in CD20 + cells from the peripheral blood (PB) and synovial fluid (SF), simultaneously obtained from 10 RA and 8 psoriatic arthritis (PsA) patients. Dynamic interactions between B cells negatively immunoselected from buffy coats, and 12h TNF-a-activated human umbilical vein endothelial cell (HUVEC) monolayers were studied in a two-parallel plate flow chamber. To study molecules involved in the B-cells-HUVEC dynamic interaction, B cells were preincubated with monoclonal antibodies (mAbs) anti-CD20 or blocking mAbs anti- L-selectin, VLA-4 and ICAM-1; and HUVEC, with anti-vascular adhesion molecule (VCAM)-1.

Results:

Flow cytometry analysis showed that the VLA-4 surface expression level in B-cells from SF in both RA (105±30%) and PsA (135±45%) patients was not significantly different with respect to PB (considered 100%). Interestingly, the surface expression level of ICAM-1 was significantly higher in SF relative to PB, in both RA (280±85%;) and PsA (300±65%) patients, while L-selectin surface expression diminished in SF compared to PB in RA (40±5%) and PsA (45±5%). In flow chamber experiments, no differences were observed in the process of rolling when B cells were incubated with anti-CD20 antibodies, or with blocking mAbs anti-L-selectin and anti-ICAM-1 with respect to cells incubated with mAb matching controls. However, the presence of blocking anti-VLA-4 mAb or anti-VCAM-1 mAbs abrogated the interaction of B cells with activated endothelial cells.

Conclusion:

These results suggest that 1) B-cells with increased ICAM-1 expression and decreased L-selectin expression are preferentially recruited in the inflamed synovial microenvironment; and 2) the integrin VLA-4, vis-à-vis its endothelial counter receptor VCAM-1, plays a key role in the initial process of B-cell extravasation to inflammatory foci.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-integrin-very-late-antigen-4-plays-a-key-role-in-the-recruitment-of-b-cells-at-the-inflammatory-foci/