HIGH CD40 MEMBRANE EXPRESSION IN AIDS-RELATED LYMPHOMA B-CELL LINES IS ASSOCIATED WITH THE CD45RA(-LEVELS OF ITS SOLUBLE FORM IN CULTURE SUPERNATANTS(), CD45RO(+), CD95(+) PHENOTYPE AND HIGH)

CD40 is a membrane glycoprotein expressed on normal and neoplastic B l ymphocytes. Stimulation through CD40 regulates important cellular func tions, but the effects depend on its membrane density. While extensive studies have characterized CD40 in non-Hodgkin lymphomas of immunocom petent individuals, little is known on the characteristics of this mol ecule in lymphomas arising in immunocompromised hosts. The aim of this study was to characterize the pattern of CD40 expression in an in vit ro model constituted by AIDS small non-cleaved lymphoma (SNCCL) cell l ines. The analysis of CD45 isoforms, a group of molecules alternativel y spliced during B cell differentiation, has been chosen to correlate this process to the number of CD40 molecules per cell in these cell li nes. Since Apo 1/Fas expression is upregulated on B lymphocytes after CD40 ligation and this expression is functionally relevant, we wanted to know whether a different CD40 pattern in AIDS-SNCCL cell lines coul d influence CD95 expression. We have shown that 3 of these cell lines (PA 682, Es III, and HBL-2) have high membrane CD4O expression (>100,0 00 molecules/cell); they release large amounts of soluble CD40 (sCD40) in culture supernatants (>500 mu g/ml), are CD45RA/RO double labelled , and express the Apo 1/Fas (CD95) antigen. On the contrary, low CD40 membrane antigen cell lines (BRGlgA, HBL-2, NC 71, AS 283A, and LAM C3 +, < 50,000 molecules/cell) release low amounts of sCD40 (<300 mu g/ml ), are CD45RA(+) but 0045RO(-) and do not express CD95. EBV has no rol e in CD40 and CD45 isoform behaviour, because EBV superinfection of th e EBV negative, low membrane CD40 HBL-2 cell line does not modify CD40 membrane expression, sCD40 production, or CD45 isoform and CD95 expre ssion. Our data suggest that membrane CD40 in AIDS-SNCCL cell lines mi ght be a key element in the regulation of their pathophysiology by inf luencing the expression of CD45 isoforms and of CD95, and by the relea se of its soluble form. (C) 1997 Wiley-Liss, Inc.