2. Pathology and biology

#### 2.1. Pathogenesis

DLBCL is composed of large B cells with a diffuse growth pattern arising from mature B cells at different stages of differentiation. Normal B cell development takes place in the bone marrow and results in the transformation of a B-progenitor cell into mature B cell. Mature B cells have undergone immunoglobulin VDJ gene rearrangement and express a complete IgM antibody molecule on the cell surface [4]. After release from the bone marrow, antigen naïve mature B cells are exposed to antigen in the interfollicular area of the secondary lymphoid tissues. Majority then migrate into the germinal center. Mature antigen exposed B cells proliferate in the center of a primary follicle to form the germinal center. The centroblasts mature into centrocytes as they transition into light zone of the germinal center. In the germinal center, B cell undergoes class-switch recombination and somatic hypermutation. Centroblasts are thought to give rise to germinal center B cell (GCB) DLBCL. After transition through the germinal center, B cells can become memory cells or plasmablasts which undergo further development to become plasma cells. Plasmablasts are thought to give rise to activated B cell like (ABC) DLBCL [4].
