Cytogenetic and immunologic identification of clonal expansion of stem cells into T and B lymphocytes in one Atomic-bomb survivor

Blood. 1995 Sep 15;86(6):2106-12.

Abstract

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.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aged
  • B-Lymphocyte Subsets / pathology*
  • Chromosomes, Human, Pair 13 / ultrastructure
  • Chromosomes, Human, Pair 4 / ultrastructure
  • Chromosomes, Human, Pair 5 / ultrastructure
  • Chromosomes, Human, Pair 6 / ultrastructure
  • Clone Cells / pathology*
  • Female
  • Hematopoietic Stem Cells / pathology
  • Hematopoietic Stem Cells / radiation effects*
  • Humans
  • Immunophenotyping
  • Interleukin-2 / biosynthesis
  • Japan
  • Karyotyping
  • Nuclear Warfare*
  • Radiation Injuries / genetics*
  • Radiation Injuries / pathology
  • Survival
  • T-Lymphocyte Subsets / pathology*
  • Translocation, Genetic*

Substances

  • Interleukin-2