Localization in situ of costimulatory molecules and cytokines in B‐cell non‐Hodgkin’s lymphoma

Abstract

Costimulatory molecules are essential in cognate interactions between T and B lymphocytes. To study the prerequisites of functional interactions between malignant B cells and intermingled T cells in B-cell non-Hodgkin's lymphomas (B-NHL), we examined the expression of CD40, CD80 and CD86 and their ligands CD40 ligand (CD40L, CD154), CD28 and CTLA4 (CD152) using immunohistochemistry and confocal laser scanning microscopy. Almost all mucosa-associated lymphoid tissue (MALT) NHL were positive for CD40 and CD80 and in nine out of 14 cases were positive for CD86. The majority of follicle centre cell lymphomas (FCCL) expressed CD40, but were heterogeneous in their expression of CD80 and CD86. Most diffuse large cell lymphomas (DLCL) were CD80+, but lacked expression of CD86. These patterns reflect the differences in phenotype of normal marginal-zone B cells (as counterparts of MALT NHL) and germinal centre cells (as counterparts of FCCL and DLCL). Counter-receptors on T cells were detectable in 13 of 14 MALT NHL, 12 of 16 FCCL but only occasionally in DLCL (three of 12 cases). A subgroup of FCCL was identified with T-cell expression of CD40L, CD28 and CTLA4 simultaneously with strong expression of CD40 and CD86 on the tumour B cells. These results indicate that MALT NHL and a subset of FCCL are most optimally equipped for functional interactions with T cells. This may be supported by the demonstration of cytokine production - mainly in T cells - in MALT NHL [interleukin-2 (IL-2), interferon-gamma (IFN-gamma), IL-10] and FCCL (IL-2, IFN-gamma) and to a lesser extent in DLCL.

CD80 (B7.1) is expressed on both malignant B cells and nonmalignant stromal cells in non‐Hodgkin lymphoma

“…1) as well as previously published studies (8)(9)(10)(11). Additionally, although the level of expression of CD80 as measured by flow cytometry cannot be directly correlated with expression assessed by IHC, the low level of expression observed by flow cytometry analysis (expression index of 14.9 AE 11.6) is consistent with the low intensity of staining observed by IHC (independent H-scores of 119 AE 80 and 122 AE 87).…”

“…CD80 expression in follicular non-Hodgkin lymphoma (NHL) has been previously analyzed in several small studies by immunohistochemical (IHC) analyses (8)(9)(10)(11). These studies utilized frozen tissue sections due to the lack of an anti-CD80 antibody reagent capable of specifically detecting CD80 on formalin-fixed, paraffin-embedded tissue sections.…”

Expression of CD86 and increased infiltration of NK cells are associated withHelicobacter pylori-dependent state of early stage high-grade gastric MALT lymphoma

“…Study using a murine model demonstrated that Th-1 response and CD8+ CTLs activity were strongly inhibited in the presence of persistent gastric H pylori infection [29] . Moreover, activated CD8+ CTLs may compete with CD56 (+) NK cells and downregulate the function of the latter [17] . Besides regulating the differentiation of CD8+ CTLs, CD56 (+) NK cells may have an equally important role in immune regulation, where they limit the host response to foreign antigens and prevent autoimmunity [18] .…”

“…The dependence on T-cells for the growth of malignant B-cell clones may explain the tendency of early-stage low-grade MALT lymphomas to remain localized and to regress after H pylori eradication. Expression of co-stimulatory molecules, including CD80 (B7.1), CD86 (B7.2), and their ligands, has been demonstrated in gastric MALT lymphoma cells [17] . The presence of the co-stimulatory marker CD86 (B7.2) on lymphoma cells may promote T-cell-mediated neoplastic B cell proliferation.…”

Molecular pathways in follicular lymphoma

“…The ligands, CD28/CD152 (CTLA4) for CD80/CD86 and CD40L (CD154) for CD40, are expressed by intratumoral T cells. 86,87 FDCs express ICAM1 and VCAM1, the counterstructures for LFA-1 (CD11a/ CD18) and VLA-4 (CD49d/CD29) present on FL cells. 88,89 Although FDCs may also present native Ag to the FL cells, immunohistochemical staining using four FL-derived soluble Igs did not reveal binding to any structures or cells in the corresponding lymphoma tissues.…”