Proliferative response of mantle cell lymphoma cells stimulated by CD40 ligation and IL-4

Mantle cell lymphoma (MCL) is a tumor of intermediate-size, IgM+, IgD+ B ce lls derived from the mantle zone of the germinal center. Little is known ab out its specific immunologic features or responsiveness to T cell-derived s ignals. In this work, we evaluated the proliferation and cell cycle propert ies of freshly isolated MCL cells after CD40 ligation, in the absence and p resence of interleukin 4 (IL-4). In each MCL case examined, there was a mar ked growth-enhancing effect of these two stimuli characterized by improved viability, augmented expression of Ki-67, and induction of the proliferatin g cell nuclear antigen (PCNA). Cyclin D1 was expressed throughout the cell cycle in MCL cells induced to enter S phase. From these investigations, we conclude that the biology of MCL B lymphocytes is affected by CD154 (CD40 l igand) and IL-4, two signals usually provided by CD4(+) T cells. The capaci ty to manipulate the activation and cell cycle state of MCL cells by these specific immunological stimuli may be exploited to confer susceptibility to chemotherapy agents and develop novel therapies in this disease.