SIGNAL-TRANSDUCTION VIA HUMAN-LEUKOCYTE ANTIGEN CLASS-II MOLECULES DISTINGUISHES BETWEEN CORD-BLOOD, NORMAL, AND MALIGNANT ADULT B-LYMPHOCYTES

Cord blood is increasingly used for hematopoietic stem cell transplant ation since less severe graft-versus-host disease has been reported le ading to the notion that cord blood is ''naive.'' Human leucocyte anti gen (HLA) class II molecules are expressed throughout B lymphocyte ont ogeny (except the plasmocytes), are responsible for antigen presentati on, and can also transmit signals. Cord blood B stimulate an allogenei c 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 relocal ization of protein kinase C (PKC) isoenzymes alpha and beta II was det ected along with tyrosine kinase activation and proliferation. However , in contrast to resting adult B, generation of an intracellular calci um ([Ca++](i)) flux and rapid aggregation were not detected. To addres s the question of whether or not HLA-DR signals throughout B lymphocyt e ontogeny, we extended this study to include malignant adult B (B chr onic lymphocytic leukemia [B-CLL], B mantle cell lymphoma, and B large cell leukemia). Tyrosine kinase activation and proliferation were obs erved in all these cell populations, albeit in the absence of [Ca++](i ) flux or an increase in PKC. HLA-DR therefore transmits signals throu ghout B lymphocyte ontogeny, although different signaling pathways are initiated in adult vs. fetal vs. malignant B. The lack or intracellul ar [Ca++](i) flux in both cord blood and malignant B lymphocytes may r epresent a feature of HLA class II signaling at a particular stage of differentiation, although the downregulation of PKC clearly distinguis hes between cord blood B and B-CLL.