Mouse Spleen: Anatomy, Functions, and Pathology

The mouse spleen plays a crucial role in immune defense and blood regulation, making it a key focus of biomedical research. Its structure and function closely resemble those of the human spleen, making it a valuable model for studying immunity, hematopoiesis, and disease pathology.

A closer look at its anatomy, specialized tissue structures, and pathological changes provides insights into its physiological significance and how diseases affect its function.

Anatomical Layout

The mouse spleen is a small, elongated organ in the upper left quadrant of the abdominal cavity, adjacent to the stomach and pancreas. Unlike the rounded human spleen, the murine spleen is distinctly elongated and flattened, with a dark red to purplish hue due to its high vascularization. A thin but resilient fibrous capsule, composed primarily of dense connective tissue, provides structural integrity while allowing for expansion and contraction in response to physiological demands. This capsule extends inward, forming trabeculae that create a supportive framework for the internal compartments.

Beneath the capsule, the spleen is divided into red pulp and white pulp, which are interspersed rather than existing as distinct layers. The red pulp, comprising most of the spleen’s mass, consists of splenic cords and venous sinuses that facilitate blood cell movement. Specialized endothelial cells line these sinuses, allowing selective passage of cells between circulation and splenic tissue. The white pulp, in contrast, is organized around central arterioles and consists of periarteriolar lymphoid sheaths (PALS) and lymphoid follicles. These structures, embedded within the red pulp, support immune processes.

The splenic vasculature is highly specialized, with the splenic artery branching into smaller arterioles that supply both pulp regions. Blood flow follows an open and closed circulation model, with some blood passing directly into venous sinuses while other portions enter the splenic cords before re-entering circulation. This arrangement facilitates interaction between circulating cells and the splenic microenvironment. The venous drainage system converges into the splenic vein, linking the spleen to liver metabolism and systemic blood regulation.

Major Functions

The mouse spleen plays a critical role in immune surveillance, blood filtration, and serving as a reservoir for hematopoietic components. Its distinct microarchitecture allows efficient interaction between circulating cells and splenic tissue.

Immune Response

The spleen is central to adaptive and innate immunity, serving as a site for antigen presentation and lymphocyte activation. The white pulp contains dense aggregations of lymphoid tissue, including PALS rich in T cells and lymphoid follicles populated by B cells. These structures facilitate immune responses by enabling antigen-presenting cells, such as dendritic cells and macrophages, to interact with lymphocytes.

A 2021 Frontiers in Immunology review highlighted how splenic macrophages and dendritic cells capture circulating antigens and present them to naïve T and B cells, initiating immune responses. The spleen also serves as a site of extramedullary hematopoiesis under pathological conditions like severe infections or bone marrow failure.

Blood Filtration

The red pulp filters aged, damaged, or abnormal erythrocytes from circulation. Splenic cords and venous sinuses create a selective barrier that only deformable, healthy red blood cells can traverse. Senescent or structurally compromised erythrocytes are retained and phagocytosed by splenic macrophages.

A Blood (2020) study detailed how this filtration mechanism is particularly relevant in conditions such as sickle cell disease and hereditary spherocytosis, where abnormal red blood cells are prematurely removed, contributing to anemia. The spleen also plays a role in iron recycling by breaking down hemoglobin from degraded erythrocytes and storing iron in macrophages for transport to the bone marrow.

Blood Reservoir

The spleen serves as a reservoir for erythrocytes, platelets, and leukocytes, which can be rapidly mobilized in response to physiological demands. This function is particularly evident in rodents, where the spleen contracts to release stored cells during acute stress or hemorrhage.

Research in The Journal of Physiology (2019) demonstrated that the murine spleen can store up to 20% of the total circulating red blood cell volume, which can be released during hypoxia or blood loss. This process is mediated by smooth muscle fibers in the splenic capsule and trabeculae, which contract in response to sympathetic nervous system activation. The spleen also contributes to platelet homeostasis by sequestering and releasing platelets as needed, impacting clotting and wound healing.

Red And White Pulp Structures

The mouse spleen consists of red and white pulp, interwoven throughout the organ to support its physiological roles. Mice exhibit a predominance of red pulp, reflecting their reliance on the spleen for hematological regulation. This structural organization ensures blood encounters both filtration and immune processing functions in a coordinated manner.

The red pulp’s splenic cords and venous sinuses enable blood cell passage and retention. The cords, composed of reticular connective tissue, house macrophages and stromal cells that maintain circulating erythrocytes. Venous sinuses, lined by specialized endothelial cells with discontinuous basement membranes, create a filtration barrier that selectively removes aged or damaged erythrocytes while permitting viable cells to re-enter circulation. The open circulation model enhances this filtration by exposing blood cells to macrophage-rich environments before they return to the vascular system.

Interspersed within the red pulp, the white pulp is organized around central arterioles and serves as a framework for lymphoid aggregates. PALS, which surround these arterioles, are densely populated with T cells, while adjacent lymphoid follicles contain B cell clusters. This arrangement ensures compartmentalized cellular interactions while maintaining proximity to the vascular supply. The marginal zone, a transitional area between red and white pulp, directs blood-borne components toward either filtration pathways or immune processing regions. Specialized stromal cells in the white pulp support the retention and organization of lymphoid populations.

Common Pathological Findings

The mouse spleen is susceptible to various pathological changes affecting its structure and function. Splenomegaly, or spleen enlargement, is common in experimental models and is often associated with increased hematopoiesis, congestion, or infiltrative diseases. This condition can result from excessive red blood cell sequestration, abnormal protein deposition, or proliferative disorders that disrupt normal splenic architecture. Chronic splenomegaly may lead to mechanical stress on the splenic capsule, increasing the risk of rupture.

Fibrosis within the spleen can arise from chronic inflammation or toxin exposure. Progressive collagen deposition in the red pulp impairs blood filtration by restricting erythrocyte movement through the splenic cords. Over time, fibrotic remodeling reduces the spleen’s ability to regulate circulating blood cell populations, leading to cytopenias or compensatory extramedullary hematopoiesis. Histological examination often reveals thickened trabeculae and disorganized reticular networks, indicators of underlying systemic disease.

Histological Analysis Methods

Microscopic examination of the mouse spleen provides insights into its structure and pathological changes. Histological analysis relies on specialized staining techniques and imaging methods to differentiate cellular components and assess tissue integrity. Proper sample preparation is essential, with formalin or paraformaldehyde fixation commonly used to preserve morphology. Sectioning is typically performed with a microtome, producing thin slices for analysis.

Hematoxylin and eosin (H&E) staining remains the standard method for general histological assessment, clearly visualizing red and white pulp regions. H&E staining highlights dense lymphoid aggregates in the white pulp and the sinusoidal network of the red pulp. Specialized stains, such as Periodic Acid-Schiff (PAS) for polysaccharides or Prussian blue for iron deposits, help identify pathological changes like fibrosis or hemosiderin accumulation. Immunohistochemistry (IHC) adds specificity by targeting proteins associated with immune cells, vascular structures, or extracellular matrix components. Markers like CD3 for T cells, B220 for B cells, and F4/80 for macrophages delineate immune populations within the spleen.

Fluorescence microscopy and confocal imaging enhance visualization by allowing co-localization of multiple markers, providing detailed insights into cellular interactions. Flow cytometry complements histological analysis by quantifying immune cell subsets in dissociated splenic tissue, offering a dynamic perspective on cellular composition. Advances in digital pathology have enabled automated image analysis, improving accuracy and reproducibility in histological assessments. These techniques collectively enhance understanding of spleen morphology and function, aiding both research and disease modeling.