Aged mice exhibit distinct B cell precursor phenotypes differing in activation, proliferation and apoptosis.
Senescence in murine models is associated with a reduction, albeit heterogeneous, in bone marrow pre-B cells. We have categorized aged BALB/c mice into two phenotypes based on their patterns of pre-B/pro-B cell loss. Each phenotype is characterized by distinct responses to the growth cytokine IL-7 and capacity for survival in vitro. A 'moderate' loss of late-stage pre-B cells (25-80%) coincided with decline in proliferation to rmIL-7. This was also associated with a decrease in the frequency of pro-B cells which increased phosphotyrosine content upon IL-7 stimulation, an indicator of early activation events. A 'severe' loss of pre-B cells (>80%) resulted in a reduced pro-B cell pool which retained normal activation and proliferative responses to IL-7. B cell precursors from aged mice with severe alterations in B lymphopoiesis displayed increased susceptibility to apoptosis in comparison to both aged mice with moderate B cell precursor loss and young mice. Conceivably, during senescence, aged mice may initially accumulate B cell precursors which are poorly responsive to IL-7. Progressively, these refractory B cell precursors may be eliminated via apoptosis; however, the remaining limited pool of B cell precursors retains the capacity to respond to IL-7 stimulation.
Van der Put
Elaine
E
Department of Microbiology and Immunology, University of Miami School of Medicine, P.O. Box 016960 R138, Miami, FL 33101, USA.
Sherwood
Erin M
EM
Blomberg
Bonnie B
BB
Riley
Richard L
RL
D000375:Aging / Q000276:immunology*; D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D002455:Cell Division / Q000276:immunology; D016130:Immunophenotyping; D015851:Interleukin-7 / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D010766:Phosphorylation; D014443:Tyrosine / Q000378:metabolism
D015851:Interleukin-7; D014443:Tyrosine