Frozen in time

I need to say something about differentiation. The whole of life is about stem cells turning into differentiated cells. The most obvious stem cell is the fertilized egg, which has to differentiate into every tissue in the body: liver cells, blood cells, brain cells, skin cells, bowel cells and bladder cells. Within a given tissue there are stem cells committed to different paths of differentiation. For example, in the bone marrow pluripotenial stem cells differentiate in different directions to make lymphocytes, monocytes, erythrocytes, neutrophils, eosinophils, basophils, dendritic cells, platelets, etc.

A true stem cell carries all the possible genes; differentiation involves switching some off and some on. A bone marrow stem cell destined to become a neutrophil goes through stages of differentiation and cell division. It is first a myeloblast, then a promyelocyte, then a myelocyte, then a metamyelocyte then a non-segmented polymorph and finally a neutrophil which struts and frets its hour upon the stage and then is seen no more.

In most cancers, the process of differentiation is interfered with. A cell becomes frozen in time; incapable of differentiating further. In acute myeloblastic leukemia, cells are frozen at the myeloblast stage.

The differentiation of the B lymphocyte was described yesterday, but in different terms. A B lymphocyte becomes committed to make a particular antibody by all that rearrangement of the V, D and J genes. The next stage is to enter the germinal center of the lymph node where somatic mutation takes place, making the antibody the best fit possible for the antigen. From there the B cells either migrates back to the bone marrow to become a plasma cell where it secretes its antibody, or it circulates in the blood as a memory cell.

Throughout the 1990s the great debate was about whether the CLL cell was frozen as a pre-germinal center cell or a post-germinal center cell. There were believers on both sides. Tomorrow I will tell you who won.