Lymph Node Anatomical Regions and Cellular Composition
Lymph nodes are organized into three main anatomical regions: the cortex (superficial cortex), the paracortex (deep cortex), and the medulla, each containing distinct cellular populations that support specialized immune functions. 1, 2
1. Cortex (Superficial Cortex)
The cortex represents the outermost region of the lymph node and serves as the primary B-cell zone.
Cellular Composition:
- B lymphocytes are the predominant cell type, organized into follicular structures 1, 2
- Follicular dendritic cells (FDCs) form networks within B-cell follicles to present antigen and support B-cell activation 3
- Germinal center B cells (centroblasts and centrocytes) appear in secondary follicles during active immune responses 3
- Tingible body macrophages are present within germinal centers to phagocytose apoptotic B cells 1
- Subcapsular sinus macrophages line the floor of the subcapsular sinus, capturing antigens from afferent lymph 4, 3
Structural Features:
- Contains primary follicles (resting B-cell aggregates) and secondary follicles with germinal centers during immune activation 2
- The subcapsular sinus sits immediately beneath the capsule, where afferent lymph first enters 4, 3
2. Paracortex (Deep Cortex)
The paracortex is the T-cell-rich zone located between the cortex and medulla, serving as the primary site for T-cell activation and interaction with antigen-presenting cells.
Cellular Composition:
- T lymphocytes (both CD4+ and CD8+ subsets) are the dominant population 1, 2
- Dendritic cells (interdigitating dendritic cells) present antigens to T cells and initiate adaptive immune responses 1, 3
- High endothelial venules (HEVs) are specialized blood vessels through which circulating lymphocytes enter the node 4, 5
- Fibroblastic reticular cells (FRCs) form the reticular meshwork scaffold and create functional microenvironments 2, 3
- Paracortical macrophages provide additional antigen presentation and immune regulation 1
Structural Features:
- Contains the paracortical cords, which are the functional units stretching from medullary cords to B-cell follicle bases 5
- HEVs are concentrated in this region, facilitating lymphocyte recruitment from blood 4, 5
- The lymphatic labyrinths in the deep cortex serve as exit routes for lymphocytes migrating into efferent lymph 4
3. Medulla
The medulla is the innermost region of the lymph node, organized into medullary cords and sinuses that facilitate lymph drainage and contain plasma cells.
Cellular Composition:
- Plasma cells (antibody-secreting B cells) are concentrated in medullary cords 1, 2
- Medullary macrophages line the medullary sinuses and filter lymph before it exits 1, 4
- LYVE-1 positive sinus reticular cells (lymphatic endothelial cells) form networks within medullary sinus lumens 4
- Memory B and T lymphocytes transit through this region 1
- Stromal reticular cells provide structural support for medullary cords 2
Structural Features:
- Medullary sinuses are interconnected channels that converge toward the hilum where efferent lymphatics exit 4
- Medullary cords are cellular strands between sinuses containing plasma cells and other immune cells 1, 2
- This region serves as the final filtration point before lymph exits the node 4
Functional Integration
The three-compartment organization creates distinct immune microenvironments: B cells encounter and respond to antigen in the cortex, T cells are activated in the paracortex through interactions with dendritic cells arriving from peripheral tissues, and plasma cells in the medulla secrete antibodies into efferent lymph 2, 3. The fibroblastic reticular cell network spans all three regions, providing structural scaffolding and creating conduits for rapid soluble antigen delivery to immune cells 3, 5.
Clinical Pitfall:
When evaluating lymph node pathology, understanding normal compartmentalization is essential—disruption of this architecture (loss of cortex-paracortex-medulla distinction) often indicates malignant lymphoma rather than reactive hyperplasia 2.