Expression, distribution, and biochemistry of human CD39. Role in activation-associated homotypic adhesion of lymphocytes.
The distribution, biochemical properties, and function of CD39 were characterized with the use of a new mAb termed 400. CD39 is an acidic (isoelectric point, approximately 4.2) glycoprotein of Mr approximately 78,000, containing approximately 24 kDa of N-linked oligosaccharide but no detectable O-linked sugars. CD39 was not expressed by resting blood T, B, or NK cells, neutrophils, or monocytes, but was expressed on activated NK cells, B cells, subsets of T cells, and T cell clones. Furthermore, the pattern of expression of CD39 was distinct from the "classic" activation Ag CD25 and CD71, inasmuch as it was expressed long after expression of CD25 and CD71 had returned to basal levels. CD39 was easily detectable on EBV-transformed B cell lines but was absent from pre-B and non-EBV-transformed B cell lines, most myeloid cell lines, and leukemic T cell lines. In lymphoid tissues, germinal center cells expressed little or no CD39, whereas some paracortical lymphocytes and most macrophages and dendritic cells were positive. CD39 was strongly expressed by endothelium in all tissues examined, including skin, and was present on some, but not all, endothelial cell lines propagated in vitro. Interestingly, mAb binding to certain epitopes on CD39 induced rapid homotypic adhesion that appeared to involve LFA-1 (CD11a/CD18), but was morphologically and kinetically distinct from that induced by PMA. Anti-CD39 mAb also induced homotypic adhesion in an CD11/CD18-EBV-transformed B cell line derived from a patient with severe leukocyte adhesion deficiency. This adhesion was unaffected by EDTA, suggesting that this pathway of anti-CD39-induced homotypic adhesion was not mediated by any of the known integrins. These studies suggest that CD39 is involved in the cellular signaling that regulates adhesion.
Kansas
G S
GS
Division of Tumor Immunology, Dana-Farber Cancer Institute, Boston, MA 02115.
Wood
G S
GS
Tedder
T F
TF
D000251:Adenosine Triphosphatases; D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000737:chemistry / Q000276:immunology / Q000502:physiology*; D000943:Antigens, Differentiation / Q000737:chemistry / Q000276:immunology / Q000502:physiology*; D001081:Apyrase; D001386:Azides / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000276:immunology / Q000502:physiology*; D002460:Cell Line; D003513:Cycloheximide / Q000494:pharmacology; D003572:Cytochalasins / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D003847:Deoxyglucose / Q000494:pharmacology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1; D007526:Isoelectric Point; D007694:Killer Cells, Natural / Q000276:immunology; D008213:Lymphocyte Activation; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology; D008214:Lymphocytes / Q000166:cytology* / Q000276:immunology; D008970:Molecular Weight; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; D001386:Azides; D015815:Cell Adhesion Molecules; D003572:Cytochalasins; C065289:ICAM2 protein, human; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1; D003609:Dactinomycin; D003513:Cycloheximide; D003847:Deoxyglucose; D000251:Adenosine Triphosphatases; D001081:Apyrase; C067869:CD39 antigen; D013755:Tetradecanoylphorbol Acetate