ANTIADHESIVE SIGNALS ARE MEDIATED VIA MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II MOLECULES IN NORMAL AND NEOPLASTIC HUMAN B-CELLS - CORRELATION WITH B-CELL DIFFERENTIATION STAGE

We show that major histocompatibility complex (MHC) class II molecules on B cells transmit signals which regulate adhesion in a negative man ner. Engagement of MHC class II molecules with antibodies results in d etachment of B cells previously bound to interferon-gamma-activated hu man umbilical cord venous endothelial cells. This process depends on m etabolic energy, active signaling and protein tyrosine kinase activity . The adhesion pathway influenced by this signaling event is neuramini dase sensitive. The anti-adhesive signaling program is activated in B cell lines with a mature phenotype, e.g. normal B cells from spleen an d tonsil. In contrast, cell lines with a pre-B cell phenotype and norm al B cells from peripheral blood are refractory to MHC class II-mediat ed regulation of adhesion. These results extend to neoplastic cells fr om patients with lymphoproliferative diseases representing different s tages of B cell maturation. These results suggest that MHC class II-me diated signals regulate B cell adhesion in a developmentally programme d fashion; this might have implications for clinical behavior of B cel l malignancies.