Thymocyte and B-Cell Death Without DNA Fragmentation

In mammals there are several cell renewal systems including the epidermis, the intestinal epithelium, and blood cells, in which a number of cells are generated every day, while a similar number of cells are lost due to cell death. In the hematopoietic system, for example, most blood cells, once they mature, die at various intervals with different life-spans for each lineage cells; mature neutrophils die within 2-3 days, whereas denucleated mature erythrocytes are totally discarded every 120 days by splenic or liver macrophages. Among hematopoietic lineages, most lymphoid cells are also short-lived, indicating they have rather short life-spans, though some of them are long-lived memory cells. The most characteristic aspect of the lymphoid cell fate is their repertoire generating mechanism. In both T and B lymphocytes, their extensively diversified repertoire is characteristically produced by their enormous proliferating activities and by consequent massive cell death, leaving only a minor population with an appropriately selected repertoire specificity. In T lymphocytes, the site for repertoire generation is the thymus, and for B lymphocytes the bone marrow and the germinal center. In this chapter we carefully examine in situ cell death of thymocytes and B cells at the germinal center and discuss their cell death mechanism.