Figure 1.

The origin of the three most-common mature B-cell lymphoid neoplasms according to their normal B cells counterparts. Naïve B cells develop in the bone marrow where they generate a B-cell receptor (BCR) and circulate to the secondary lymphoid organs (spleen or lymph nodes) where they are activated in contact with a specific antigen, resulting in a formation of a germinal center. Antibody affinity maturation occurs in the dark zone where B cells extensively proliferate and undergo somatic mutations of the immunoglobulin variable region, and in the light zones, where B cells interact with T_FH and APC cells and are selected for a specific clone that has the highest affinity for the antigen. MCL, DLBCL (ABC- and GCB-), and FL are NH B-cell lymphomas arise from mature B-cells in the secondary lymphoid organ. In most of the cases, FL, DLBCL, and MCL express the transmembrane protein CD20 (that is acquired from pre-B to memory stages), targeted by Rituximab (anti-CD20) and harbor different intrinsic factors leading to a constitutive mTORC1 activity. Corresponding intrinsic factors leading to aberrant mTORC1 activation are indicated. APC, antigen presenting cell; T_FH, follicular helper T cell; Ig; immunoglobulin; BCR, B-cell receptor; FL, Follicular Lymphoma; DLBCL, Diffuse Large B Cell Lymphoma; GCB-DLBCL, germinal-center B-cell-DLBCL; ABC-DLBCL, Activated B-cell-DLBCL; MCL, Mantle Cell Lymphoma.