title: Expression of costimulatory molecules in low-grade mucosa-associated lymphoid tissue-type lymphomas in vivo.
abstract: B-cell lymphomas of mucosa-associated lymphoid tissue (MALT) type develop against a background of chronic inflammation and have functional autoantigen receptors. Because they respond to environmental factors in vivo, the expression of costimulatory molecules, which play a key role in the differentiation of normal B-lymphocytes and in T-/B-cell interaction, may be critical in early MALT-type lymphoma pathogenesis until further chromosomal aberration leads to progression. We found a high number of tumor-infiltrating T-lymphocytes (TITLs) in all low-grade MALT-type lymphomas. The TITLs in low-grade lymphomas were activated and expressed a memory and immunocompetent phenotype. Reverse transcriptase-polymerase chain reaction analyses and immunohistochemistry confirmed the presence of CD40-ligand and Fas-ligand in 80% of low-grade lymphomas. In contrast to the TITLs, the tumor B cells did not express CD40-ligand or Fas-ligand in vivo or in vitro. Moreover, the cytokine profile in vivo suggested a Th2/Th3-weighted profile (interleukin-10, interleukin-13, transforming growth factor beta(1)) rather than Th1-weighted (interferon-gamma, interleukin-2). By interphase fluorescence in situ hybridization analysis the translocation t(11;18)(q21;q21) was found in four of nine (44%) cases studied. Interestingly, there was a four times higher proliferation and survival rate of purified t(11;18)-positive tumor B cells in vitro, although there were no significant profile differences from the TITLs in vivo. The finding of essential costimulating molecules in low-grade MALT-type lymphomas in vivo indicates a locally directed cognate T-/B-cell interaction. Consequently, a potentially equipped inflammatory background may not only determine the fate of autoreactive B-cells, but is also crucial to lymphoma maintenance and progression.
authors.affiliation: Institute of Pathology, University of Würzburg, Würzburg, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Knörr
authors.forename: C
authors.initials: C
authors.lastname: Amrehn
authors.forename: H
authors.initials: H
authors.lastname: Seeberger
authors.forename: A
authors.initials: A
authors.lastname: Rosenwald
authors.forename: S
authors.initials: S
authors.lastname: Stilgenbauer
authors.forename: G
authors.initials: G
authors.lastname: Ott
authors.forename: H K
authors.initials: HK
authors.lastname: Müller Hermelink
authors.forename: A
authors.initials: A
authors.lastname: Greiner
mesh_terms: D016175:B-Lymphocyte Subsets; D015153:Blotting, Western; D019013:CD40 Antigens / Q000378:metabolism; D002880:Chromosomes, Human, Pair 11; D002887:Chromosomes, Human, Pair 18; D016207:Cytokines / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D018442:Lymphoma, B-Cell, Marginal Zone / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D010641:Phenotype; D012313:RNA / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D016176:T-Lymphocyte Subsets; D014178:Translocation, Genetic; D019014:fas Receptor / Q000378:metabolism
chemical_list: D019013:CD40 Antigens; D016207:Cytokines; D019014:fas Receptor; D012313:RNA