Cytogenetic and immunologic identification of clonal expansion of stem cells into T and B lymphocytes in one Atomic-bomb survivor.
Chromosome aberration frequency in peripheral blood lymphocytes is elevated in radiation-exposed people, and identical karyotypic changes are not infrequently encountered in one blood sample as well as in separate samples from the same donor. Such clonal propagation originates either from a single immature stem cell able to expand and differentiate into several cell types or from a single mature lymphocyte able to expand after antigen stimulation in vivo. In the present study, a total 71 T-lymphocyte and 58 B-lymphocyte colonies were established from one atomic-bomb survivor, who showed a persistent clonal aberration t(4;6), t(5;13) in phytohemagglutinin culture of peripheral lymphocytes. Nearly 10% of the colonies (6 T-lymphocyte and 7 B-lymphocyte colonies) showed the same chromosome abnormality. Southern blot analyses of the T-cell-receptor or Ig heavy-chain gene showed all different rearrangement patterns among T- or B-lymphocyte colonies, respectively. Thus, the chromosome aberration occurred in a precursor cell before differentiation into T and B lineages and was not derived from monoclonal proliferation of mature T or B lymphocytes in the periphery. To confirm the issue, cells from erythroid burst-forming unit (BFU-E) colonies were examined by the chromosome-painting method. Two translocations, one between chromosomes 5 and 13 and the other between chromosomes 4 and one of group C, perfectly consistent with the t(4;6), t(5;13), were found in about 10% of the cells. The results imply that a single stem cell of an adult is capable of generating long-lived myeloid and lymphoid progeny amounting to several percent of the total population of circulating lymphocytes and hematopoietic progenitors.
Kusunoki
Y
Y
Department of Radiobiology, Radiation Effects Research Foundation, Hiroshima, Japan.
Kodama
Y
Y
Hirai
Y
Y
Kyoizumi
S
S
Nakamura
N
N
Akiyama
M
M
D000368:Aged; D016175:B-Lymphocyte Subsets / Q000473:pathology*; D002882:Chromosomes, Human, Pair 13 / Q000648:ultrastructure; D002894:Chromosomes, Human, Pair 4 / Q000648:ultrastructure; D002895:Chromosomes, Human, Pair 5 / Q000648:ultrastructure; D002896:Chromosomes, Human, Pair 6 / Q000648:ultrastructure; D002999:Clone Cells / Q000473:pathology*; D005260:Female; D006412:Hematopoietic Stem Cells / Q000473:pathology / Q000528:radiation effects*; D006801:Humans; D016130:Immunophenotyping; D007376:Interleukin-2 / Q000096:biosynthesis; D007564:Japan; D007621:Karyotyping; D009689:Nuclear Warfare; D011832:Radiation Injuries / Q000235:genetics* / Q000473:pathology; D013534:Survival; D016176:T-Lymphocyte Subsets / Q000473:pathology*; D014178:Translocation, Genetic
D007376:Interleukin-2