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Updated: Jun 4, 2026
Depletion and Reconstitution of Macrophages in Mice
Published on: August 1, 2012
Alterations in marginal zone macrophages and marginal zone B cells in old mice
Shirin Z Birjandi1, Jill A Ippolito, Anand K Ramadorai
1Program for Immunology and Aging, Graduate Program in Cell Biology, Neurobiology and Anatomy, Loyola University Chicago Medical Center, Maywood, IL 60153, USA.
Abstract:
Marginal zones (MZs) are architecturally organized for clearance of and rapid response against blood-borne Ags entering the spleen. MZ macrophages (MZMs) and MZ B cells are particularly important in host defense against T-independent pathogens and may be crucial for the prevention of diseases, such as streptococcal pneumonia, that are devastating in older patients. Our objective was to determine whether there are changes in the cellular components of the MZ between old and young mice. Using immunocytochemistry and a blinded scoring system, we observed gross architectural changes in the MZs of old mice, including reduction in the abundance of MZMs surrounding the MZ sinus as well as disruptions in positioning of mucosal addressin cell adhesion molecule 1 (MAdCAM-1)(+) sinus lining cells and metallophilic macrophages. Loss of frequency of MZMs was corroborated by flow cytometry. A majority of old mice also showed reduced frequency of MZ B cells, which correlated with decreased abundance of MZM in individual old mice. The spleens of old mice showed less deposition of intravenously injected dextran particles within the MZ, likely because of the decreased frequency in MZMs, because SIGN-R1 expression was not reduced on MZM from old mice. The phagocytic ability of individual MZMs was examined using Staphylococcus aureus bioparticles, and no differences in phagocytosis were found between macrophages from young or old spleens. In summary, an anatomical breakdown of the MZ occurs in advanced age, and a reduction in frequency of MZM may affect the ability of the MZM compartment to clear blood-borne Ags and mount proper T-independent immune responses.
Insights
Aging causes anatomical breakdown in splenic marginal zones (MZs), reducing marginal zone macrophages (MZMs) and MZ B cells. This age-related decline impairs the spleen's ability to clear blood-borne antigens and mount immune responses.
Area of Science:
- Immunology
- Aging Research
- Spleen Biology
Background:
- Marginal zones (MZs) in the spleen are critical for clearing blood-borne antigens and initiating immune responses.
- Marginal zone macrophages (MZMs) and MZ B cells are vital for defense against T-independent pathogens, particularly relevant in older individuals susceptible to infections like streptococcal pneumonia.
Purpose of the Study:
- To investigate age-related changes in the cellular composition and architecture of splenic marginal zones.
- To compare the frequency and function of MZMs and MZ B cells in young versus old mice.
Main Methods:
- Immunocytochemistry and blinded scoring were used to assess MZ architecture in old and young mice.
- Flow cytometry quantified the frequency of MZMs and MZ B cells.
- Intravenous dextran particle deposition and Staphylococcus aureus bioparticle phagocytosis assays evaluated splenic function.
Main Results:
- Old mice exhibited significant architectural disruptions in MZs, including reduced MZMs and altered positioning of sinus lining cells and metallophilic macrophages.
- Flow cytometry confirmed a lower frequency of MZMs in older mice, which correlated with reduced MZ B cells.
- While MZMs from old mice showed no difference in phagocytic capacity, reduced MZMs led to decreased deposition of dextran particles in the spleen's MZ.
Conclusions:
- Advanced age is associated with an anatomical breakdown of the splenic marginal zone.
- A reduced frequency of MZMs in aged spleens compromises the clearance of blood-borne antigens and the effectiveness of T-independent immune responses.
