Gastric
B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) develops in the context of chronic
inflammation caused by Helicobacter pylori
infection. Most pathophysiological features of the early stages of MALT lymphomagenesis can be reproduced by experimental
infection of BALB/c mice with Helicobacter species. We have previously shown that
MALT lymphomas are infiltrated by T-helper cell type 2-polarized T cells and that human and murine
tumor B cells carry polyreactive
surface immunoglobulins. Using the murine model of the disease, in this study we show that explanted
tumor B cells proliferate upon stimulation with the same panel of self and foreign
antigens that are recognized by their surface
antibodies.
Tumor cell proliferation is strongly enhanced by the presence of intratumoral CD4(+) T cells in a CD40/
CD40L-independent manner. A large proportion of
tumor-infiltrating CD4(+) T cells are CD25(+)FoxP3(+) regulatory T cells (Tregs) with highly suppressive activity, which are recruited by the
tumor cells through secretion of the Treg-attracting
chemokines CCL17 and CCL22. The depletion of CD25(+) cells was as efficient as CD4(+) T cell depletion in blocking
tumor growth in vitro and in vivo. In conclusion, our data suggest that B-cell receptor-derived signals cooperate with T-helper cell signals in driving the progression of
MALT lymphoma, providing an explanation for the unique
antigen dependence of this B-cell
malignancy.