Model for CLL B-cell tumor growth and antibody production by nonmalignant B cells due to aberrant expression of CD40L in CD40⁺ CLL B cells. (A) Autoligation of CD40 by CD40L at the CLL B-cell surface, or possibly secreted by the same cell, results in intracellular tumor cell signaling. (B) Ligation of CD40 in one CLL B cell by CD40L in a nearby CLL cell results in tumor cell activation, proliferation, and inhibition of apoptosis. This process is likely to depend also on cytokines derived from nearby T lymphocytes. (C) Ligation of CD40 in a bystander B cell by CLL B-cell–derived CD40L results in activation, differentiation, and antibody production by the nonmalignant cell. As in (B), this process is likely to depend on cytokines derived from nearby T lymphocytes, and on the presence of antigen.