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What is a lymph node?

Lymph nodes (LNs) are small, bean shaped glands located throughout the entire body. They form a part of the lymphatic system which transports nutrients and waste around the body. LNs serve as a major player in our immune system and houses many white blood cells (WBCs) which help to monitor the fluid that passes through a LN in search of any "bad stuff" present (such as an infection, tumor, waste products etc). If encountered, they can then activate a response in the body to help remove the unwanted offender.

The (simplified) big picture...

In very simple terms, you can think of the LN as a training camp where soldiers (WBCs) go to be taught "who/what is bad" and how to react if they ever encounter the villain in the future. During bootcamp, the soldiers enter training camp and are assigned to various troops based on their special skills (lymphocytes (B-cells & T-cells), plasma cells, macrophages and others). The troops have a designated area in the lymph node where their soldiers train (cortex, paracortex, medullary region or sinuses).

B cells go to the superficial cortex and form follicles. T cells can help to activate B-cells, thus they tend to be located surrounding the B-cell follicles, but are deeper in the cortex (paracortical region). If the troops come in contact with a "bad guy" (called an antigen), then they can become activated by working together to start a war to fight off the "bad guy". After activation, the B-cells mature to become plasma cells which function to produce antibodies against the antigen (think of it as a way to mark all of the "bad guys" so the soldiers know what to attack). Plasma cells will move from the follicles in the cortex to deeper within the LN in the medulla where they line up along the medullary sinusoids. They then release their antibodies into the efferent lymphatic fluid so it can go to other LNs around the body to alert them that there is a "bad guy" around that needs to be taken care of.


Check out the overall schema of a lymph node bootcamp below












Primary location: Superficial cortex forming follicles

Function: Bind to "bad guy" antigen to initiate a response for the eventual antibody production against the antigen

Centroblast B-cells -

  • Responsible for lymphocyte proliferation and somatic hypermutation of IGH gene

  • Found mostly in dark zone of GC

  • Immature B cells with frequent mitoses

  • Large- 3-4 x size of small lymphocytes

  • 1-3 peripheral nucleoli

  • Large vesicular nuclei

  • Rim of cytoplasm

  • "Tattoo": B-cell markers, polytypic immunoglobulins, CD10, BCL-6 (does not express BCL-2)

Centrocyte B-cells -

  • More mature B cells than centroblasts

  • Found in light zone of GC with follicular dendritic cells

  • Small to intermediate size

  • Cleaved, hyperchromatic nuclei

  • Small or absent nucleolus

  • Rare mitoses

  • Scant cytoplasm


CD4+ helper T cells (most of the T cells)

  • Small, round, hyperchromatic

  • Smaller and more uniform than the small centrocytes

  • "Tattoo": CD3, CD4, CD10, Bcl-6, CXCL13, PD1/CD279

CD8+ cytotoxic T cells (small subset of the T c ells)

  • Small, round, hyperchromatic

  • Smaller and more uniform than the small centrocytes

  • "Tattoo": CD3, CD8



  • Oval or twisted vesicular nuclei

  • Faint or pink cytoplasm

  • "Tattoo": CD68, CD163

Tingible-body macrophages

  • Subset of histiocytes with abundant pale cytoplasm with karyorrhectic nuclei

  • Have a "starry sky" pattern when prominent

Follicular dendritic cells

  • Forms a meshwork of cells with long cytoplasmic processes

  • Found in light zone of GC with centrocytes

  • "Tattoo": CD21, CD23, CD35


  • The area immediately surrounding the GC

  • Composed of concentric layers of small naive B cells that have not been exposed to "bad guy" yet.

Outer cortex- Follicles & Germinal centers= B cells
Inner/Paracortex= T cells
Medulla- cords, sinuses, trabecula= Plasma cells


LNs are surrounded by a thin fibrous capsule. Broadly speaking, the LN is divided into 4 regions (cortex, paracortex, medullary region and sinuses. Lymphatic fluid will enter the lymph node through a lymphatic vessel (afferent vessel) into the subcapsular sinus which then divides into cortical and medullary sinuses until eventually exiting through the efferent lymphatic vessel at the hilum. The hilum also contains the arteries and veins which enter and exit the lymph node and brings the circulating WBCs to the LN.

The superficial cortex contains many follicles consisting of mostly B cells. In a "normal" LN, follicles should be located around the periphery, evenly spaced, variably sized. As the B-cells mature and are activated (due to infection or another cause), the follicles will change from a quiescent (resting) primary follicle to secondary follicles with germinal centers.

During the follicular B-cell activation process, a dark zone (containing the proliferating B cells) and a light zone (where the B cells further specialize into plasma cells) can be appreciated. Surrounding the periphery of the germinal center is what is referred to as the Mantle Zone. The mantle zone contains small unchallenged B cells. Check out my other post about follicles for a more in-depth look at the follicular structure and maturation process

Surrounding the mantle zone is another light staining zone referred to as the Marginal Zone. The marginal zone contains postfollicular memory B cells that are derived after stimulation of recirculating cells from T cell dependent antigens. Marginal zones are mostly seen in the spleen at the interface of lymphoid (white) and red pulp and rarely seen in lymph nodes (except mesenteric LNs).

T cells and dendritic cells (macrophages) are located deeper within the cortex in the paracortical zone. The medulla contains medullary cords (activated B cells, plasma cells) and medullary sinuses (lymph, more macrophages, plasma cells and reticular cells).

What can cause a lymph node to be swollen?

LNs are usually less than 1 cm in size. There are many reasons for a lymph node to be enlarged. Depending on the pattern of enlargement (whether a single LN or diffusely throughout the body) and whether the LN is tender (painful to touch), clinicians can narrow down the likely cause of the enlargement and may be able to start treatment. For a definitive diagnosis, clinicians can order imaging of the LN (via ultrasound, CT scan etc) or can biopsy or completely excise the lymph node and send the specimen to pathologists for a definitive diagnosis.

Most commonly, pathologists are asked to evaluate enlarged lymph nodes for the following reasons:

  • Rule out metastatic disease (cancer that has left its primary site and moved to a lymph node/other areas in the body)

  • Rule out lymphoma (cancer of the lymphocytes in a lymph node)

  • Assess for infection (Viral- measles, rubella, varicella (chicken pox), mumps, EBV or CMV (mononucleosis), AIDS/HIV. Bacterial- streptococcus (strep throat), rickettsia (lyme disease), syphilis etc).


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