Lymphocytes life-span

Also J. Sprent and D. F. Tough. Lymphocyte life-span and memory. Science, 265, 1395-1400, 1994. 

Lymphocytes are of two sizes smaller lymphocytes, with a diameter of 6-8 pm, and larger lymphocytes, with a diameter up to 18 pm. They are found not only in blood, but in lymph and in every tissue of the body. Larger lymphocytes are believed to be cells that differentiate into T and B lymphocytes when activated by specific antigens. The life span of lymphocytes may vary from a few days to many years. Lymphocytes have been suggested as potential carriers for transporting macromolecules, particularly DNA, to other cells. Low molecular weight exogenous substances can be introduced into lymphocytes by electrical breakdown methods. 

In somatic cell gene therapy, a DNA sequence is inserted into a somatic cell to correct a mutation. Cells may be removed from the patient for manipulation and subsequent reinsertion (ex vivo therapy), or they may be manipulated without removal fi om the patient (in vivo therapy). Ideally, cells with a very long life span (e.g., bone marrow stem cells) are treated, but other cells (e.g., lymphocytes) are sometimes more practical targets. 

Produced by lymphoid tissue. Lymphocytes represent about 20% of the WBCs in adults they have a long life span (sometimes several years). They probably serve as memory cells for the immune system. These mononuclear cells may be small, agranular structures (T and B cells) or large, granular cells (NKCs). Different types of T cells may only be differentiated by their cell-surface markers (CD markers - clusters of differentiation). CD markers are identified using labelling antibodies... 

B lymphocytes will be eliminated during continuous culture because these cells have a short life span in culture. Commercially available myeloma cells for hybridoma production have mutations in one of the enzymes of the salvage pathway of purine nucleotide biosynthesis. Hybridoma cells are cultured in medium that forces the cells to utilize the salvage pathway for nucleotide synthesis. The mutated myeloma cells or hybridization products of two myeloma cells will die in this selection medium since they are incapable of nucleotide synthesis under these propagation conditions. However, myeloma cells that have fused to the B lymphocytes derived from the spleen of the immunized animal will have an intact salvage pathway and will survive in the selection medium. Thus, only the B lymphocytes-myeloma hybridomas will survive prolonged culture in the selection medium. 

Transformed and tumorigenic cells are different from normal cell lines in that they are not usually anchorage dependent. They exhibit a spherical shape, increased life span and lateral diffusivity of membrane proteins, decreased cell receptors and membrane proteins, and a different cytoskeletal structure. The decrease in the concentration of the cell adhesion molecules in the cell membrane of these cells causes the anchorage independence. Transformed cell lines also do not assemble a normal ECM. It is important to note that some cell lines (e.g., lymphocytes) that are normally anchorage dependent can be induced and then adapted to become anchorage independent. This is of tremendous importance to recombinant protein production as discussed later, because the scale-up of suspension cultures is easier than that of anchorage-dependent cell lines. 

Immature T cells produced in the bone marrow ultimately migrate to the thymus, where they both expand and mature into immunologically competent cells (see Fig. 98 ). A variety of cytokines, including IL-2, IL-4, and lL-7, facilitate lymphopoiesis, whereas others such as transforming growth factor-/ may decelerate this process. T lymphocytes are probably the longest lived hematopoietic cell, as there is experimental evidence that the life span of some is more than 10 years. 

As screening capacity in the U.S. National Cancer Institute s P388 lymphocytic leukemia (PS) test increased in the 1965-1968 period it began to have a very beneficial impact on the success of our research directed at the discovery of marine animal antineoplastic constituents. The early (6) and more recent 13) evolutionary direction of the NCI antineoplastic and cytostatic evaluation systems has been reviewed. By 1968 extracts of B. neritina reached the confirmed active level and consistently allowed over a 100% increase in life span. Bioassay guided isolation was begun with the PS in vivo system and supplemented from 1975 on with the PS in vitro cell line. The in vivo and in vitro activity... 

Recent studies have shown that T-lymphocytes of peritoneal origin possess both NeuSAc and Neu5Gc on their surface (Kaufmann et al 1981). Since this is the first demonstration of Neu5Gc on murine lymphocytes, it would be of special interest to learn, whether this derivative has the same properties in respect to migration behaviour and life span of cell. 

The ideal of any vaccine is to provide life-long protection to the individual against disease. Immunological memory (Chapter 14) depends upon the survival of cloned populations of small B and T lymphocytes (memory cells). These small lymphocytes have a lifespan in the body of ca. 15-20 years. Thus, if the immune system is not boosted, either by natural exposure to the organism or by re-immunization, then immunity gained in childhood will be attenuated or lost completely by the age of 30. Those vaccines which provide only poor protection against disease have proportionately reduced time-spans of effectiveness. Yellow fever vaccination, which is highly effective, must therefore be repeated at 10-year intervals, whilst typhoid vaccines are only effective for 1-3 years. Whether or not immunization in childhood is boosted at adolescence or in adult life depends on the relative risks associated with the infection as a function of age. 

---