Re: What is the role of apoptosis in the thymus?

Carrie,

You ask several important questions so I will have to think carefully to be sure I get you started on finding an answer.

Apoptosis has become a field unto itself. There is a great volume of literature now being published in many journals dealing with the molecules and signal cascades that control this kind of cell death. It is such an important kind of cell death that we would have deformed bodies if there were defects in its ability to happen. For example, the defect of cleft palate occurs during development of the baby if something prevents apoptosis of the epithelial cells that cover the two sided of the boney palate as it grows from side to side in the face. Contact between epithelial cells at this time triggers those epithelial cells on the right and left side to die so that a single (not cleft) palate results.

It might seem strange to talk about a cleft palate in context with discussion of the thymus but it is closer than you would believe. In the human embryo back in the pharynx where the tonsils will develop are structures called branchial arches and clefts (this is during the time when an embryo looks like it might have gills, thus the term branchial).

The thymus is an epithelial organ that forms from two tongues of epithelium that grow down from the right and left, 3rd and forth branchial clefts and arches. These epithelial anlage of thymus form lobes and lobules in the anterior mediastinum (just under the part of your sternum at the root of the neck and near the top of your heart).

The epithelial thymus gets populated by hematopoietic cells especially cells destined to be lymphocytes and eventually 99% of the cells will be lymphocytes that we call T-cells because of their important association with the thymus. B-cells are labeled that because they are more prevalent in bone marrow but there are also B-cells in the thymus but only about 1% of the cells are committed to that lineage.
The thymus has a cortex and a medulla. The cortex has more cells in it and there are further layers to it. The newest cells committed to T-cell development are found out near the surface of the thymus where cell division is rapid. As these cells differentiate they move centrally toward the medulla and leave from that place.

Since less than 5% of the T-cells generated in the thymus live to leave and 95% of the newly divided cells don't you can understand that there is an awful lot of apoptosis taking place in the thymus. There are specific chapters of information discussing just one kind of apoptotic situation for T-cells so my review here must be considered pretty superficial but I will give it a try in defining the kinds that take place. Cells that mutate during rapid division may undergo apoptosis if they no longer express surface molecules that enable them to detect "self" antigens. Those self antigens might be on the epithelial stromal cells or on dendritic cells or mononuclear cells that migrated into the thymus. During division T-cells may mutate one or both of the molecules involved in recognizing antigens so that they bind antigen too weakly, too tightly. Either of those conditions could cause apoptosis. T- cells become "educated" to recognize two types of Major Histocompatibility MHC antigens while they are in the thymus called Class I and Class II MHC antigens. Whether these t-cells see the right MHC molecule could regulate whether or not it apoptoses. In addition to this there are other molecules called costimulatory molecules, for want of a better word, that must be present as well for if they are not the cell will miss seeing them and will apoptose (CD40-CD40-Ligand; CD44-Hyaluronate, CD28-B7 are receptor pairs that carry out this "costimulatory function")

Now, are you completeley confused? Or, are you hungry for more information and maybe some pictures to put this all together. If so, I recommend you go visit my Immunology Lecture notes. The first link IMMUNE will take you to the lecture notes at the main page. The second link CENTRAL will take you right to the thymus page of my notes. If you want some other notes to compare go back to the main page and scroll down. You will find several other sites with lecture notes that can help you find what you need.

All the best.

Art Anderson