Service d'hématologie biologique, hôpital Avicenne et UPRES EA 1625, université Paris 13, 125, route de Stalingrad, 93009 Bobigny cedex.
- Key words: differentiation, B-lymphocyte, B-cell lymphoma.
- Page(s) : 345-59
- Published in: 2000
Secondary immune response is elaborated within secondary lymphoid organs. Microanatomy of secondary lymphoid organs showed relationships between B-cell areas and B-cell differentiation. Primary follicles and mantle zone of secondary follicles contain recirculating IgM+ IgD+ resting B-lymphocytes. T-cell dependant humoral response is iniated in T-cell area with formation of B-blast foci. Some of the B-blast migrate into an adjacent primary follicle, expand rapidly and form the germinal centre with its dark zone containing centroblasts ant its light zone containing centrocytes. Centroblastes are submitted to somatic mutations of the variable region of the immunoglobulin genes and isotypic switch, and differentiate into centrocytes. Centrocytes die by apoptosis unless the antigen presented by follicular dendritic cells, positively selects them. Then, centrocytes differenciate in memory B-cell which are located in the marginal zone or in plasma cells. Three phases humoral T-dependant immune response can be recognised: a pre-germinal, a germinal and a post-germinal phase.
Current classification systems of B-cell lymphomas tried to systematically make reference to the normal cell counterpart. It is noteworthy that the recognition of the pre-germinal, germinal or post-germinal origin of tumoral B-cell is an important feature. Mantle cell lymphomas are originated from pre-germinal B-cells. Fifty percent of chronic lymphocytic leukemia is derived from a post-germinal B-lymphocyte. Lymphoplasmocytoid and marginal zone lymphomas are derived from a post-germinal B-lymphocyte. Follicular lymphoma and Burkitt's lymphoma are from germinal centres. Most of diffuse large B-cell lymphomas are from a germinal or a post-germinal origin. However, primary mediatinal B-cell lymphoma are probably from a pre-germinal origin. Hodgkin's lymphomas are derived from a B-lymphocyte and correspond to two entities, the Hodgkin's lymphoma with lymphocyte predominance and the "classical Hodgkin's disease". Hodgkin's lymphoma with lymphocyte predominance are originated from a germinal centre B-lymphocyte submitted to antigenic selection. The classical Hodgkin's disease probably derives from a germinal centre B-lymphocyte with a crippling immunoglobulin gene rearrangement that has escaped to apoptosis.
These examples highlight the relationships between B-cell differenciation and B-cell lymphomagenesis, which molecular mechanism is probably dependent on the differentiation stage of the non tumoral starting point.