Differential contribution of Wiskott-Aldrich syndrome protein to selective advantage in T-and B-cell lineages

A Konno, T Wada, SH Schurman, EK Garabedian… - Blood, 2004 - ashpublications.org
A Konno, T Wada, SH Schurman, EK Garabedian, M Kirby, SM Anderson, F Candotti
Blood, 2004ashpublications.org
Somatic mosaicism because of in vivo reversion has been recently reported in a small
number of patients affected with Wiskott-Aldrich syndrome (WAS). Flow cytometry analysis of
WAS protein (WASP) expression has shown that these patients carried revertant cells only
among T lymphocytes. Here, we have used high-resolution capillary electrophoresis to
analyze genomic DNA from highly purified cells of one of these patients and detected
revertant sequences also within the B-cell fraction. The demonstration of revertant cells …
Abstract
Somatic mosaicism because of in vivo reversion has been recently reported in a small number of patients affected with Wiskott-Aldrich syndrome (WAS). Flow cytometry analysis of WAS protein (WASP) expression has shown that these patients carried revertant cells only among T lymphocytes. Here, we have used high-resolution capillary electrophoresis to analyze genomic DNA from highly purified cells of one of these patients and detected revertant sequences also within the B-cell fraction. The demonstration of revertant cells among both T and B lymphocytes in this patient is consistent with the reversion event having occurred in a common lymphoid progenitor. However, although WASP-expressing T cells showed selective advantage and were readily detectable in the periphery of the mosaic patient, revertant B lymphocytes remained below the detection threshold of flow cytometry. These findings suggest that, contrary to T cells, differentiation and survival of B lymphocytes is minimally dependent on WASP.
ashpublications.org