Regulation of CD44-hyaluronan interactions in Burkitt's lymphoma and Epstein-Barr virus-transformed lymphoblastoid B cells by PMA and interleukin-4

In this study, we investigated the regulation of CD44-hyaluronan (HA) inter actions in a panel of EBV+ Burkitt's lymphoma (BL) and lymphoblastoid B cel l lines (B-LCL) generated by in vitro EBV transformation of normal human B cells. The results show that among B cell mitogens, phorbol la-myristate 13 -acetate (PMA) alone induced strong HA recognition in EBV+ BL-30/B95-8 cell s. Among the cytokines that affect B cell growth and differentiation, IL-4 alone induced HA recognition in BL-30/B95-8 cells. Attempts to delineate th e molecular mechanism for this increased HA adhesion in BL-30/B95-8 cells r evealed an enhanced expression of CD44 H, isoforms containing V3, V6, and V 9 exons, alterations in the splicing pattern of the V4 exon, and the increa sed electrophoretic mobility of the CD44 H protein. In contrast, the abilit y to recognize ECA was not observed in B-LCL cells stimulated with either P MA or IL-4, even though these cells respond to IL-4, as observed by upregul ation of CD23 expression. The molecular pathways that regulate CD44 express ion and CD44-mediated HA binding may be selectively inactivated in B-LCL ce lls. These results may have implications with respect to the generation and spread of B cell tumors. (C) 1999 Academic Press.