Signal transduction via human leucocyte antigen class II molecules distinguishes between cord blood, normal, and malignant adult B lymphocytes.
Cord blood is increasingly used for hematopoietic stem cell transplantation since less severe graft-versus-host disease has been reported leading to the notion that cord blood is "naive." Human leucocyte antigen (HLA) class II molecules are expressed throughout B lymphocyte ontogeny (except the plasmocytes), are responsible for antigen presentation, and can also transmit signals. Cord blood B stimulate an allogeneic response, and this property is believed to indicate the presence of a class II-associated peptide. In this study we examined the capacity of cord blood B to transmit signals via HLA-DR. Activation and relocalization of protein kinase C (PKC) isoenzymes alpha and betaII was detected along with tyrosine kinase activation and proliferation. However, in contrast to resting adult B, generation of an intracellular calcium ([Ca++]i) flux and rapid aggregation were not detected. To address the question of whether or not HLA-DR signals throughout B lymphocyte ontogeny, we extended this study to include malignant adult B (B chronic lymphocytic leukemia [B-CLL], B mantle cell lymphoma, and B large cell leukemia). Tyrosine kinase activation and proliferation were observed in all these cell populations, albeit in the absence of [Ca++]i flux or an increase in PKC. HLA-DR therefore transmits signals throughout B lymphocyte ontogeny, although different signaling pathways are initiated in adult vs. fetal vs. malignant B. The lack of intracellular [Ca++]i flux in both cord blood and malignant B lymphocytes may represent a feature of HLA class II signaling at a particular stage of differentiation, although the downregulation of PKC clearly distinguishes between cord blood B and B-CLL.
Laboratoire d'Immunogénétique Humaine, INSERM U396, Institut Biomédical des Cordeliers, Paris, France.
F
F
Garban
J P
JP
Truman
J
J
Lord
B
B
Drénou
J
J
Plumas
M C
MC
Jacob
J J
JJ
Sotto
D
D
Charron
N
N
Mooney
D000328:Adult; D000367:Age Factors; D017951:Antigen Presentation / Q000502:physiology*; D001402:B-Lymphocytes / Q000276:immunology*; D002449:Cell Aggregation; D002454:Cell Differentiation; D002455:Cell Division; D004789:Enzyme Activation; D005312:Fetal Blood / Q000166:cytology / Q000276:immunology*; D006684:HLA-DR Antigens / Q000276:immunology*; D006801:Humans; D007231:Infant, Newborn; D007527:Isoenzymes / Q000378:metabolism; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation; D016393:Lymphoma, B-Cell / Q000276:immunology / Q000473:pathology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000276:immunology / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000276:immunology*; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000032:analysis; D011493:Protein Kinase C / Q000378:metabolism; D064546:Protein Kinase C beta; D051571:Protein Kinase C-alpha; D011499:Protein Processing, Post-Translational; D015398:Signal Transduction
D006684:HLA-DR Antigens; D007527:Isoenzymes; D019000:Phosphotyrosine; C496628:PRKCA protein, human; D011493:Protein Kinase C; D064546:Protein Kinase C beta; D051571:Protein Kinase C-alpha