Telomeres are structures at the ends of linear eukaryotic chromosomes. Mammalian telomeres consist of hexanucleotide (TTAGGG)n repeats and several protein components.
In the absence of compensatory mechanisms, telomeres shorten with each cell division due to incomplete replication of chromosomal termini.
Telomeres are crucial for several functions, including the maintenance of chromosomal integrity and replicative capacity. When telomeres reach a critically short length, or lose functional integrity due to other alterations in the telomeric complex, cells are prone to apoptotic death and/or replicative senescence, a state in which no further cell division occurs.
Human T and B cells undergo telomere shortening with age, as has been observed for other somatic cells. The functional consequences of this shortening for human immune function are unknown.
The best-characterized compensatory mechanism for the maintenance of telomere length in the face of cell division is mediated by telomerase, an enzyme that can synthesize terminal telomere repeats. Telomerase is a unique enzyme consisting of an RNA-template component that encodes telomeric DNA and a catalytic-protein component that is an RNA-dependent DNA polymerase or reverse transcriptase.
Telomerase is expressed at high levels in germ-line cells and most cancer cells. Most normal somatic cells express little or no telomerase enzymatic activity and, therefore, undergo progressive telomere shortening with cell division.
The function of T and B cells in the immune response is highly dependent on extensive cell division and clonal expansion. In contrast to many other somatic-cell lineages, T and B cells express high levels of telomerase activity at regulated stages of development and after the activation of mature T and B cells. Telomerase might have a role in at least partially compensating for telomere loss in dividing lymphocytes.
A definitive role for telomerase or telomere-length change has not been established during normal human immune responses. However, several lines of evidence indicate that abnormalities in telomerase and telomere-length maintenance can affect somatic-cell function, including immune function. Such evidence has been provided by mouse models of telomerase deficiency and by a recently characterized human genetic syndrome, dyskeratosis congenita, that is marked by abnormal telomerase function.
Telomeres are the structures at the ends of linear chromosomes. In mammalian cells, they consist of hexanucleotide (TTAGGG) repeats, together with many associated proteins. In the absence of a compensatory mechanism, dividing cells undergo gradual telomere erosion until a critical degree of shortening results in chromosomal abnormalities and cell death or senescence. For T and B cells, the ability to undergo extensive cell division and clonal expansion is crucial for effective immune function. This article describes our current understanding of telomere-length regulation in lymphocytes and its implications for immune function.
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