Intra-bone marrow bone marrow transplantation rejuvenates the B-cell lineage in aged mice.
Age-related reductions in the frequency and absolute number of early B lineage precursors in the bone marrow of aged mice have been reported. Reversal of B-cell lineage senescence has not been achieved. Age-related impairment of the B-cell lineage is caused by the decreasing functionality of hematopoietic and B lineage precursors, and reduced efficacy of bone marrow stromal cells that constitute the bone marrow microenvironment. To induce rejuvenation of aged B cells, we injected whole bone marrow from young donors to irradiated aged recipients through the tibia and analyzed B-cell development and immune responsiveness. In aged mice, we found significant reductions in the frequencies and absolute numbers of pro-B cells (B220(+)CD43(+)CD24(+)BP-1(-) and B220(+)CD43(+)CD24(int)BP-1(+)) and pre-B cells (B220(+)CD43(+)CD24(high)BP-1(+) and B220(+)CD43(-)IgM(-)IgD(-)). Intra-bone marrow bone marrow transplantation (IBM-BMT) of young marrow cells including both hematopoietic stem cells and bone marrow stromal cells reversed the reduction of pro-B cells and pre-B cells. In the periphery, the frequency and absolute number of marginal zone-B cell were not significantly different between young, old and IBM-BMT group. The frequency of follicular-B cells in the IBM-BMT group was significantly increased compared to old group. The frequency of B1a B cells in the peritoneal cavity was significantly decreased in the IBM-BMT group. Antibody production against T-independent antigens was not different among the young, the aged and IBM-BMT groups.
Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Japan.
Daisuke
D
Hida
Naoki
N
Ishiguro
Masataka
M
Haneda
Yoshiyuki
Y
Ishida
Haruhiko
H
Suzuki
Ken-Ichi
K
Isobe
D000375:Aging / Q000276:immunology*; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D016026:Bone Marrow Transplantation / Q000276:immunology*; D019070:Cell Lineage; D015552:Injections, Intralesional; D051379:Mice; D008810:Mice, Inbred C57BL; D013977:Tibia / Q000601:surgery