B cell maintenance in aged mice reflects both increased B cell longevity and decreased B cell generation.
In aged mice the population of mature peripheral B cells is maintained despite a severalfold decrease in the population of bone marrow B cell progenitors. The analysis of the rate of accumulation of 5'-bromo-2-deoxyuridine (BrdU)-labeled splenic B cells in mice fed BrdU for 8 days to 8 wk demonstrated a severalfold increase in the half-life of mature B cells in aged mice. Consistent with a role for decreased B cell turnover in maintaining the mature B cell population of aged mice, several findings indicate that fewer newly generated B cells enter the spleen from the bone marrow in aged vs young adult mice. These include 1) a fourfold decrease in the population of relatively immature splenic B cells, defined as cells that express high levels of heat-stable Ag and accumulate BrdU within 8 wk of labeling; and 2) an equivalent decrease in the population of bone marrow cells representative of later stages of B cell maturation (sIgD-sIgM(int-high)). Surprisingly, despite a four- to sixfold decrease in pre-B cells, the population of least mature bone marrow B cells (IgD-sIgM(very low)) remains intact. Because this population accumulates BrdU-labeled cells more slowly in aged mice than in younger mice, and bone marrow B cells at more mature developmental stages are diminished, it appears that in aged mice B cell development beyond the sIgM(very low) stage may be retarded and that cells, therefore, accumulate within this population.
Kline
G H
GH
Department of Immunology, Scripps Research Institute, La Jolla, CA 92037, USA.
Hayden
T A
TA
Klinman
N R
NR
D000375:Aging / Q000276:immunology*; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D001854:Bone Marrow Cells / Q000166:cytology; D001973:Bromodeoxyuridine / Q000378:metabolism; D002453:Cell Cycle / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D019070:Cell Lineage / Q000276:immunology; D002470:Cell Survival / Q000276:immunology; D007075:Immunoglobulin M / Q000032:analysis; D008213:Lymphocyte Activation / Q000502:physiology*; D051379:Mice; D011947:Receptors, Antigen, B-Cell / Q000032:analysis; D013154:Spleen / Q000166:cytology; D013234:Stem Cells / Q000166:cytology
D007075:Immunoglobulin M; D011947:Receptors, Antigen, B-Cell; D001973:Bromodeoxyuridine