Disorganization of the splenic microanatomy in ageing mice

Abstract

SummaryThe precise mechanisms responsible for immunosenescence still remain to be determined, however, considering the evidence that disruption of the organization of primary and secondary lymphoid organs results in immunodeficiency, we propose that this could be involved in the decline of immune responses with age. Therefore, we investigated the integrity of the splenic microarchitecture in mice of increasing age and its reorganization following immune challenge in young and old mice. Several differences in the anatomy of the spleen with age in both the immune and stromal cells were observed. There is an age-related increase in the overall size of the white pulp, which occurs primarily within the T-cell zone and is mirrored by the enlargement of the T-cell stromal area, concurrent to the distinct boundary between T cells and B cells becoming less defined in older mice. In conjunction, there appears to be a loss of marginal zone macrophages, which is accompanied by an accumulation of fibroblasts in the spleens from older animals. Furthermore, whereas the reorganization of the white pulp is resolved after several days following antigenic challenge in young animals, it remains perturbed in older subjects. All these age-related changes within the spleen could potentially contribute to the age-dependent deficiencies in functional immunity.

Ageing adversely affects the migration and function of marginal zone B cells

“…4f). These results have a similar trend to those previously published in BALB/c mice,9 indicating similarities between the mouse species in this regard.…”

Structural and functional changes to lymph nodes in ageing mice

“…Although the total number of BEC, FRC and LEC in aged LN was unchanged, a decrease in the total number of double‐negative (DN) cells was observed. However, their distribution within the aged LN was grossly disorganized in aged mice, in a similar manner to that seen in the spleen . Stromal cells are important for the homeostasis and migration of T cells .…”

Aged neutrophils accumulate in lymphoid tissues from healthy elderly mice and infiltrate T‐ and B‐cell zones

“…Remodeling of splenic microanatomy frequently occurs during inflammatory processes and is considered crucial for an effective immune response and for neutrophil clearance . However, splenic microarchitecture is altered in elderly mice including reduction in the MZ . We therefore immunostained spleens and lymph nodes to evaluate whether disrupted lymphoid microanatomy was accompanied by altered distribution of neutrophils.…”

“…Increased rates of mortality and morbidity in elderly humans are mainly caused by opportunistic bacterial, fungal and viral infections, which are also found in patients with neutropenia or granulocyte defects, underlining the importance of operative neutrophils for the immune system. Deterioration in organ functionality and structure also contributes directly and indirectly to the systemic low grade levels of inflammatory cytokines found in elderly hosts . However, there are no published data of neutrophil distribution in secondary lymphoid organs of healthy elderly hosts that could impact responses to pathogens.…”

“…Similarly, neutrophils also home to T cell areas in lymph nodes following an infection . Recently, disruption of the splenic microanatomy and lymph node structure has been described in healthy elderly animals . However, the role of neutrophils in lymphoid organs during healthy aging has yet to be established.…”