Cloning of phenotypically different human lymphocytes originating from a single stem cell

Area of Science:

• Immunology
• Genetics
• Radiation Biology

Background:

• Identifying the origins of distinct lymphocyte lineages (T, NK, B cells) is crucial for understanding human immune system development.
• Atomic bomb radiation exposure can induce genetic and chromosomal alterations in stem cells, providing unique markers for cellular lineage tracing.

Purpose of the Study:

• To investigate the differentiation of human T, NK, and B cells from a single adult stem cell.
• To utilize hypoxanthine guanine phosphoribosyltransferase (hprt) gene mutations and chromosome aberrations as in vivo cellular markers.
• To explore the existence of common adult stem cells for multiple lymphocyte lineages.

Main Methods:

• Cloning of mutant lymphocytes from peripheral blood of an atomic bomb survivor using 6-thioguanine resistance.
• Analysis of hypoxanthine guanine phosphoribosyltransferase (hprt) gene alterations and chromosome aberrations (20q-) in cloned cells.
• Characterization of surface phenotypes, functional properties, and TCR/Ig gene rearrangements in cloned lymphocytes.

Main Results:

• Successfully cloned T, NK, and B cells originating from a single stem cell.
• All cloned lymphocytes shared identical hprt gene alterations and the 20q- chromosome aberration.
• Despite common origin markers, cloned cells displayed diverse phenotypes and gene rearrangements, indicating post-stem cell differentiation.

Conclusions:

• The findings suggest the existence of common adult stem cells capable of differentiating into T, NK, and B lymphocytes.
• The study demonstrates the utility of hprt gene alterations as specific cellular markers for tracking lymphocyte stem cells and studying human immune cell differentiation.
• Radiation-induced genetic markers in stem cells can provide insights into early differentiation events in the lymphocyte lineage.