CYSTEINE PROTEASE CPP32, BUT NOT ICH1-L, IS EXPRESSED IN GERMINAL CENTER B-CELLS AND THEIR NEOPLASTIC COUNTERPARTS

Ich-1/Nedd2 and CPP32/YAMA are cysteine proteases related to interleuk in I-P-converting enzyme (ICE), which act as apoptosis effecters. Both molecules are expressed in T-and B-cell lines. The authors investigat ed their in vivo cellular distribution in normal and neoplastic human lymphoid tissues. Sixty-eight representative non-Hodgkin's lymphomas ( NHL) and Hodgkin's disease (HD) samples, normal lymphoid organs, and n onlymphoid tumors were analyzed by immunohistochemistry (MC). CPP32 ex pression in benign tissues was restricted to germinal center B cells, plasma cells, and a few interfollicular immunoblasts. All follicular N HLs and most diffuse large cell NHLs were CPP32 positive. Among T-cell NHLs, CPP32 expression was mainly observed in anaplastic large cell N HLs, whereas the other subtypes were less frequently positive. In cont rast, lymphoid organs displayed only weak Ich1-L expression, located i n sinusal histiocytes and thymic epithelial cells. Lymphomas were Ich1 -L negative, except for T-cell-rich B-cell NHLs, and about half of the HD samples, in which Reed-Sternberg cells (RSC) were usually Ich1-L p ositive/CPP32 negative. Extralymphoid Ich1-L reactivity was found in p articular organs like the kidney and various tumors. Western blot anal ysis confirmed the specificity of immunostaining. Neither CPP32 nor Ic h1-L expression were correlated with intratumoral DNA fragmentation, a s determined by the TUNEL assay. Altogether, these results indicate th at CPP32 is preferentially expressed in germinal centers and thus coul d be involved in B-cell maturation. The differential expression of CPP 32 and Ich1-L suggests that cysteine proteases differ in substrate spe cificities and carry out functions unrelated to apoptosis. Copyright ( C) 1997 by W.B. Saunders Company.