Development of B cells in aged mice: decline in the ability of pro-B cells to respond to IL-7 but not to other growth factors.
The process of B lymphopoiesis changes with increasing age, resulting in a severe drop in the number of pre-B cells in old mice. We have shown that the ability of freshly isolated pro-B cells to proliferate on stromal cells declines with age. In this study, we wanted to determine the reason for the diminished response of the aged pro-B cells. The functional alterations could arise from changes intrinsic to the pro-B cells or to composition of the precursor population. Changes in the composition of pro-B cells in marrow or long-term bone marrow culture system for B lymphocytes (LTBMC-B) could not account for the functional losses. We then examined the hypothesis that the diminished amount of proliferation on stromal cells was due to changes in the responsiveness to stroma-derived cytokines. The proliferation to IL-7 but not to stem cell factor (SCF) or insulin-like growth factor 1 (IGF-1) was severely impaired by 24 mo of age, independently of the concentration of IL-7 and length of culture time. The reduced IL-7 response could not be explained by an increase in the percentage of cells undergoing apoptosis; rather, a greater frequency of aged cells remained in G0/G1 after IL-7 stimulation. Furthermore, the impaired responsiveness of the aged pro-B cells is not due to diminished expression of the IL-7R alpha-chain or the common gamma-chain. Since only IL-7 responsiveness is impaired, we believe that the underlying molecular mechanism for the cellular alterations is specific to signaling through the IL-7 receptor complex.
Stephan
R P
RP
Department of Cell Biology, Neurobiology, and Anatomy, Loyola University Chicago, Maywood, IL 60153, USA.
Lill-Elghanian
D A
DA
Witte
P L
PL
D000375:Aging / Q000276:immunology*; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology; D001853:Bone Marrow / Q000276:immunology; D001854:Bone Marrow Cells; D002453:Cell Cycle / Q000276:immunology; D016923:Cell Death / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D005260:Female; D016130:Immunophenotyping; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D015851:Interleukin-7 / Q000378:metabolism / Q000494:pharmacology*; D008024:Ligands; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D008565:Membrane Proteins / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D018123:Receptors, Interleukin / Q000096:biosynthesis; D020395:Receptors, Interleukin-7; D019089:Stem Cell Factor / Q000494:pharmacology; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects; D017154:Stromal Cells / Q000276:immunology
D015703:Antigens, CD; D015851:Interleukin-7; D008024:Ligands; D008565:Membrane Proteins; D018123:Receptors, Interleukin; D020395:Receptors, Interleukin-7; D019089:Stem Cell Factor; C084881:flt3 ligand protein; D007334:Insulin-Like Growth Factor I