being sent to the bone marrow. memory b cell differentiation the gc b cells that differentiate into memory b cells are distinct from plasma cell precursors, as they show lower affinity for the antigen and do not need much help from t follicular helper cells. because of this, many scientists believe that memory b cell precursors are b cells from the light zone that were “non-positively selected.” memory b cell precursors express a transcription factor called hematopoietically-expressed homeobox protein (hhex) that drives differentiation of memory b cells from gc b cells. entering the dark zone of the germinal center any b cells that were positively selected in the light zone of the germinal center, but that did not differentiate into plasma cells or memory b cells are sent to the dark zone of the germinal center for further proliferation. these are the b cells that had intermediate affinity for the antigen. the dark zone proliferation program is regulated by foxo1 and cyclin d3. these two genes are down-regulated by strong bcr signals. therefore, when there are weak bcr signals and the gc b cell does not have high affinity for the antigen, it will be sent to the dark zone of the germinal center so that it can continue to divide rather than being secreted as a plasma cell or a memory b cell. morphology at different stages the morphology of gcs is very specific and shows properties which are characteristic for different stages of the reaction. in an early state of the reaction a network of fdcs is fully filled with proliferating b cells. later at day 4 of the reaction, gcs show a separation of two zones, the dark and the light zone. the former still contains dominantly proliferating and mutating b cells while the latter one is the area of b cell selection. these zones dissolve after 10 days of gc development which ends after about 3 weeks. medical relevance as germinal centers are important structures of the adaptive immune system, their deregulation is implied in many immune diseases, for example rheumatoid arthritis, immunodeficiency and many lymphomas like dlbcl and burkitt's lymphoma.