Expression of costimulatory molecules in low-grade mucosa-associated lymphoid tissue-type lymphomas in vivo

B-cell lymphomas of mucosa-associated lymphoid tissue (MALT) type develop a gainst a background of chronic inflammation and have functional autoantigen receptors, Because they respond to environmental factors ill vivo, the exp ression of costimulatory molecules, which play a key rot in the differentia tion of normal B-lymphocytes and in T-/B-cell interaction, may be critical in early MALT-type lymphoma pathogenesis until further chromosomal aberrati on leads to progression. We found a high number of tumor-infiltrating T-lym phocytes (TITLs) in all low-grade MALT-type lymphomas, The TITLs in low-gra de lymphomas were activated and expressed a memory and immunocompetent phen otype, Reverse transcriptase-polymerase chain reaction analyses and immunoh istochemistry confirmed the presence of CD40-ligand and Fas-ligand in 80% o f low-grade lymphomas. In contrast to the TITLs, the tumor B cells did not express CD40-ligand or Fas-ligand in vivo or ill vitro. Moreover, the cytok ine profile in vivo suggested a Th2/Th3-weighted profile (interleukin-10, i nterleukin-13, transforming growth factor beta(1)) rather than Th1-weighted (interferon-gamma, interleukin-2), By interphase fluorescence in situ hybr idization analysis the translocation t(11;18)(q21;q21) was found in four of nine (44%) cases studied. Interestingly, there was a four times higher pro liferation and survival rate of purified t(11;18)-positive tumor B cells is vitro, although there were no significant profile differences from the TIT Ls in vivo, The finding of essential costimulating molecules in low-grade M ALT-type lymphomas in vivo indicates a locally directed cognate T-/B-cell i nteraction. Consequently, a potentially equipped inflammatory background ma y not only determine the fate of autoreactive B-cells, but is also crucial to lymphoma maintenance and progression.