B Cell Maintenance in Aged Mice Reflects Both Increased B Cell Longevity and Decreased B Cell Generation

• Published in: The Journal of immunology (1950) Vol. 162; no. 6; pp. 3342 - 3349
• Main Authors: Kline, Gregory H, Hayden, Tracy A, Klinman, Norman R
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 15.03.1999
• Subjects: Aging - immunology; Animals; B-Lymphocytes - cytology; B-Lymphocytes - immunology; B-Lymphocytes - metabolism; B-Lymphocytes - physiology; Bone Marrow Cells - cytology; Bromodeoxyuridine - metabolism; Cell Cycle - immunology; Cell Differentiation - immunology; Cell Lineage - immunology; Cell Survival - immunology; Immunoglobulin M - analysis; Lymphocyte Activation - physiology; Mice; Receptors, Antigen, B-Cell - analysis; Spleen - cytology; Stem Cells - cytology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.162.6.3342

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.