B7 costimulatory molecules from malignant cells in patients with B-cell chronic lymphoproliferative disorders trigger T-Cell proliferation

BACKGROUND. B7 family molecules are involved in T-B-cell communications aft er interaction with their ligands CD28 and CD152. They play a key role in c ostimulatory mechanisms and during antigen presentation by efficient antige n presenting cells. B7 molecules are usually absent or expressed at low int ensity on B lymphocytes from healthy subjects. In this study, the authors a ddressed the questions of whether B7 molecules are expressed and modulated in vitro on malignant B lymphocytes from patients with chronic lymphoprolif erative diseases of B-cell type and whether they are able to trigger alloge nic T-cell reactions. METHODS. Malignant B cells from the peripheral blood of 32 patients with B- cell chronic lymphocytic leukemia, mantle cell lymphoma, hairy cell leukemi a, and its variant form were investigated for the expression of B7 molecule s on the cell surface and for the ability to trigger allogenic T lymphocyte s in different experimental conditions. RESULTS. Flow cytometry analysis demonstrated that freshly isolated maligna nt B cells express B7 molecules and that their expression may be up-regulat ed by the in vitro triggering of the CD40 molecule. Furthermore, freshly is olated malignant B cells induce allogenic T-cell proliferation. The in vitr o triggering of malignant B lymphocytes by CD40, alone and in combination w ith interleukin-4, elicits a strong allogenic T-cell proliferation. This T- cell proliferation is related mainly to the presence of B7 molecules on mal ignant and normal B lymphocytes. CONCLUSIONS. These findings indicate that malignant B cells are efficient a ntigen presenting cells. It might be suggested that vaccination with pulsed malignant B cells themselves or dendritic cells with in vitro preactivated tumor B cells may represent an alternative therapeutic approach in these p atients to generate an antilymphoma T-cell response in vivo. (C)T 2000 Amer ican Cancer Society.