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Blood, 15 April 2002, Vol. 99, No. 8, pp. 2760-2766
HEMATOPOIESIS
Extensive in vivo self-renewal, long-term reconstitution
capacity, and hematopoietic multipotency of Pax5-deficient
precursor B-cell clones
Christoph Schaniel,
Marie Gottar,
Eddy Roosnek,
Fritz Melchers, and
Antonius G. Rolink
From Basel Institute for Immunology, Switzerland;
Biozentrum der Universität Basel, Switzerland;
Unité d'Immunologie de Transplantation, Hôpital cantonal
universitaire de Genève, Geneva, Switzerland.
Self-renewal, pluripotency, and long-term reconstitution are
defining characteristics of single hematopoietic stem cells. Pax5 / precursor B cells apparently possess
similar characteristics. Here, using serial transplantations, with in
vitro recloning and growth of the bone marrow-homed donor cells
occurring after all transplantations, we analyzed the extent of
self-renewal and hematopoietic multipotency of
Pax5/ precursor B-cell clones. Moreover,
telomere length and telomerase activity in these clones was analyzed at
various time points. Thus far, 5 successive transplantations
have been performed. Clones transplanted for the fifth time, which have
proliferated for more than 150 cell divisions in vitro, still
repopulate the bone marrow with precursor B cells and reconstitute
these recipients with lymphoid and myeloid cells. During this
extensive proliferation, Pax5/ precursor B
cells shorten their telomeres at 70 to 90 base pairs per
division. Their telomerase activity remains at 3% of that of HEK293
cancer cells during all serial in vivo transplantations/in vitro
expansions. Together, these data show that
Pax5/ precursor B-cell clones possess
extensive in vivo self-renewal capacity, long-term reconstitution
capacity, and hematopoietic multipotency, with their telomeres
shortening at the normal rate.
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