Age-related alterations in the lymphohematopoietic and B-lineage precursor populations in NZB mice.
Significant disturbances in B lineage populations of New Zealand Black (NZB) mice have been reported, both with respect to their phenotypes as well as to their function. Notably, there is a profound age-dependent decrease in B-cell precursors in this strain of lupus prone mice. In efforts to characterize the impact of this disturbance in disease, we performed an intensive phenotypic and B-cell population analysis in young and old NZB mice. Our results revealed that there was a significant age-dependent decrease in B cell precursors at all levels of the B-cell-lineage developmental pathway. Analysis of the proliferative capacity of these cell populations showed a comparative decrease in cycling activity in the B-cell-lineage populations of old NZB mice. Furthermore, these cell subsets were much more susceptible to spontaneous apoptosis when compared with similar populations from age-matched BALB/c or young NZB mice. Since the frequency of cells that express the interleukin-7 receptor (IL-7R) declines as NZB mice age, we hypothesize that impairment of IL-7R signal transduction pathways could contribute to severe perturbations of B-cell function in aged NZB mice.
Division of Rheumatology/Allergy and Clinical Immunology, University of California at Davis, Davis, California 95616, USA.
Zhe-Xiong
ZX
Lian
Tomoyuki
T
Okada
Hiroto
H
Kita
Tom
T
Hsu
Leonard D
LD
Shultz
Kenneth
K
Dorshkind
Aftab A
AA
Ansari
Mitsuru
M
Naiki
Susumu
S
Ikehara
M Eric
ME
Gershwin
D000375:Aging / Q000276:immunology*; D000818:Animals; D017209:Apoptosis / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology* / Q000502:physiology; D002455:Cell Division / Q000276:immunology*; D019070:Cell Lineage / Q000502:physiology*; D002470:Cell Survival / Q000276:immunology; D015536:Down-Regulation / Q000276:immunology*; D005260:Female; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008814:Mice, Inbred NZB; D020395:Receptors, Interleukin-7 / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology
D020395:Receptors, Interleukin-7