B-CELL IL-7 - HUMAN B-CELL LINES CONSTITUTIVELY SECRETE IL-7 AND EXPRESS IL-7 RECEPTORS

IL-7 was originally reported as a cytokine produced by stromal cells w hich supports pre-B cell proliferation in vitro. To determine whether human B cells secrete IL-7 and express IL-7R we studied a wide panel o f B cell lines (CLS). In Northern blot analysis we detected 2.4kb IL-7 mRNA and by quantitative PCR we demonstrated IL-7 expression in 5 of 6 B CLS derived from patients with AIDS-associated Burkitt's lymphoma (AABCL), 3 of 3 CLS derived from patients with American Burkitt's lymp homa and 5 of 6 normal lymphoblastoid CLS. Only 1 of 5 African Burkitt 's lymphoma CLS and 2 of 7 EBV(-) CLS expressed IL-7. A total of 484-b p amplicons was cloned and sequenced and found to correspond to the or iginal IL-7 sequence. Constitutive IL-7 secretion was detected in 5 of 6 AABCL and in 6 of 7 normal lymphoblastoid CLS but in none of the 7 EBV(-) CLS. IL-7R expression was demonstrated in 8 of 26 CLS, none of which secreted IL-7. Our data suggest that 1) IL-7 mRNA is expressed i n malignant B cell phenotypes, which correspond to a narrow, window in the B cell differentiation pathway (pre-B, early B, intermediate B), as well as in normal lymphoblastoid B CLS. 2) IL-7 mRNA is expressed i n both EBV(+) and EBV(-) CLS, but only the EBV(+) CLS secrete IL-7. 3) B cells activated by both EBV and HIV-1 (AABCL) secrete the greatest amount of IL-7. 4) IL-7 autocrine loops are not evident since IL-7R we re detected only on CLS, which do not secrete IL-7. Our data provide t he first direct evidence of IL-7 secretion by human cells and it is ye t to be determined whether IL-7 is secreted by other cell types.