IL-12 EXPRESSION IN AIDS-RELATED LYMPHOMA B-CELL LINES

IL-12 is a 70-kDa heterodimer formed by the 40-kDa heavy chain (p40) a nd the 35-kDa light chain (p35). Twenty-five Burkitt's lymphoma cell l ines (CL) and seven normal lymphoblastoid B CL were studied. The Burki tt's CL included AIDS-associated B CL (AABCL) (7 EBV(+)/2 EBV(-)) and non-AABCL (8 EBV(+)/8 EBV(-)). Reverse transcription-PCR detected p40 in EBV(+) AABCL (7 of 7), EBV(+) non-AABCL (3 of 8), and normal lympho blastoid B CL (6 of 6) but not in EBV(-) CL (0 of 10). p35 mRNA was de tected in 30 of 30 CL. Constitutive secretion of p40 was found in 7 of 7 EBV(+) AABCL (range, 341-18,086 pg/ml) and p70 in 3 of 7 EBV(+) AAB CL (range, 25-197 pg/ml), but in only 1 of 8 EBV(+) non-AABCL and 0 of 7 normal lymphoblastoid CL. PMA stimulated p40 secretion in 7 of 7 EB V(+) AABCL and p70 secretion in 5 of 7 EBV(+) AABCL. PMA also triggere d p40 and p70 secretion in 2 EBV(+) non-AABCL and in 3 of 7 normal lym phoblastoid CL. No IL-12 secretion was detected in 10 EBV(-) CL, inclu ding EBV(-) AABCL. The CL produced IL-10, a known inhibitor of IL-12, but anti-IL-10 Abs did not neutralize IL-12. Similarly, neutralizing a nti-IFN gamma Abs or IFN gamma did not affect B cell IL-12, For IL-12R studies, reverse transcription-PCR and I-125-lL-12 binding assays wer e performed. Although all CL tested showed mRNA accumulation for one o f the IL-12R components, IL-12 binding sites were detected in only 1 o f 30 CL, Our data suggest that: 1) AABCL constitutively secrete large amounts of IL-12, contrasting with low IL-12 production by HIV-1 infec ted PBMC; 2) lack of IL-12 expression in EBV(-) AABCL suggests that in vivo exposure of & cells to HIV-1 only does not induce IL-12 secretio n and that both HIV-1 and EBV are required; 3) the autocrine-negative effect of IL-10 on IL-12 in monocytes and the enhancing effect of IFN gamma on IL-12 secretion do not apply to B cells derived from AIDS pat ients.