The heat-stable antigen can alter very late antigen 4-mediated adhesion.
The integrin very late antigen, (VLA-4) alpha 4 beta 1 and its counter receptor vascular cell adhesion molecule 1 (VCAM-1) are involved in B cell maturation and pre-B cell attachment to bone marrow stroma cells. We have analyzed whether heat-stable antigen (HSA), a marker for immature leukocytes, is involved in such cell adhesion phenomena. HSA is a glycolipid-anchored, highly glycosylated surface protein differentially expressed on cells during the maturation of both the hematopoietic and nervous systems. We found that pre-B cells lacking HSA (due to targeted disruption of both alleles) can still bind via VLA-4 to tumor necrosis factor alpha-stimulated endothelioma cells. This binding, however, cannot be blocked by an anti-VCAM-1 antibody. Restoration of HSA expression restores the inhibitable VCAM-1 binding. We also found that pre-B cells lacking HSA did not bind to the FN40 fragment of fibronectin but reexpression of HSA restored VLA-4-mediated binding to fibronectin. Thus, expression of HSA on pre-B cells modifies the binding specificity of VLA-4 for two known ligands.
Hahne
M
M
Hans-Spemann-Laboratory, Max Planck Institute for Immunobiology, Freiburg, Germany.
Wenger
R H
RH
Vestweber
D
D
Nielsen
P J
PJ
D000818:Animals; D015703:Antigens, CD / Q000502:physiology*; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology; D051927:CD24 Antigen; D002448:Cell Adhesion / Q000276:immunology / Q000502:physiology*; D002461:Cell Line, Transformed; D004727:Endothelium / Q000166:cytology; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D008562:Membrane Glycoproteins; D051379:Mice; D016029:Receptors, Very Late Antigen / Q000502:physiology*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D015703:Antigens, CD; D051927:CD24 Antigen; C497889:CD24 protein, human; C497890:Cd24a protein, mouse; D005353:Fibronectins; D008562:Membrane Glycoproteins; D016029:Receptors, Very Late Antigen; D014409:Tumor Necrosis Factor-alpha