Assessment of the role of leucocyte function-associated antigen-1 in homotypic adhesion of activated B lymphocytes.
In this study we investigated how T-cell-dependent stimuli, via interleukin-4 (IL-4) or CD40 ligation, influence homotypic B-cell adhesion when compared with induction by the T-cell-independent stimulus lipopolysaccharide (LPS). Using primary murine B cells, we found that T-cell-dependent stimulation led to increased aggregation as compared to that induced by LPS. The adhesion was to a large extent dependent on the adhesion molecule, lymphocyte function-associated antigen-1 (LFA-1). We found that activation of B cells with the mitogenic stimuli induced an increased avidity of LFA-1 for its ligand, intercellular adhesion molecule-1 (ICAM-1). The increase was stable and different from that induced by phorbol esters. Although adhesion was reduced using B cells from LFA-1(-/-) mice, aggregation occurred in response to T-cell-dependent stimuli. Our data suggest that adhesion of B lymphocytes is regulated in different modes. One is induced by antigen and leads to a transient conformational change of the LFA-1 molecule. Another is induced by mitogenic stimuli and leads to stable avidity increase of LFA-1, possibly via activation of cytoskeletal anchorage. A third is LFA-1 independent, of low avidity and is induced by T-cell-dependent stimuli.
Greicius
G
G
Karolinska Institute, Department of Cell and Molecular Biology, Stockholm, Sweden.
Tamosiunas
V
V
Severinson
E
E
D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology*; D002448:Cell Adhesion; D002478:Cells, Cultured; D005260:Female; D008213:Lymphocyte Activation; D016169:Lymphocyte Function-Associated Antigen-1 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018345:Mice, Knockout
D016169:Lymphocyte Function-Associated Antigen-1