Figure 3.

GC B-cell development and cellular derivation of B-lineage malignancies. Whereas Burkitt lymphoma seems to originate from the transformation of dark zone cells, recent evidence suggests that follicular lymphoma and germinal center B-cell type (GCB)-DLBCL may derive from the transformation of light zone cells (see text). Activated B-cell type (ABC)-DLBCL is thought to originate from light zone cells poised to undergo PC differentiation. Conventional mantle cell lymphoma (MCL) may derive from the oncogenic transformation of an antigen-activated pre-GC B cells. Multiple myeloma is a tumor of bona fide PCs. Hodgkin lymphoma is thought to originate from light zone B cells with “crippled” antigen receptors, mediastinal large B-cell lymphoma from a differentiation light zone B cell, and MZL from a post-GC marginal zone/memory B cell. Chronic lymphocytic leukemia (CLL) can have unmutated and mutated IgV genes. Several mature B-lineage malignancies show constitutive NF-κB activity, as indicated.