Lymphocyte homing receptors are

cell adhesion molecule Cell adhesion molecules (CAMs) are a subset of cell surface proteins that are involved in the binding of cells with other cells or with the extracellular matrix (ECM), in a process called cell adhesion. In essence, CAMs help cells stick to each ...

s expressed on lymphocyte cell membranes that recognize

addressin Mucosal vascular addressin cell adhesion molecule 1 (MAdCAM-1) is a protein that in humans is encoded by the ''MADCAM1'' gene. The protein encoded by this gene is an endothelium, endothelial cell adhesion molecule that interacts preferentially wi ...

s on target tissues. ''Lymphocyte homing'' refers to adhesion of the circulating lymphocytes in blood to specialized

endothelial cells The endothelium is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and the rest of the vessel ...

within

lymphoid The lymphatic system, or lymphoid system, is an organ system in vertebrates that is part of the immune system, and complementary to the circulatory system. It consists of a large network of lymphatic vessels, lymph nodes, lymphatic or lymphoid o ...

organs. These diverse tissue-specific adhesion molecules on lymphocytes (''homing receptors'') and on endothelial cells (''vascular addressins'') contribute to the development of specialized immune responses. Free lymphocytes constantly recirculate in blood after their re-entry from lymphoid tissue, via

lymphatic Lymph (from Latin, , meaning "water") is the fluid that flows through the lymphatic system, a system composed of lymph vessels (channels) and intervening lymph nodes whose function, like the venous system, is to return fluid from the tissues to ...

and

thoracic duct In human anatomy, the thoracic duct is the larger of the two lymph ducts of the lymphatic system. It is also known as the ''left lymphatic duct'', ''alimentary duct'', ''chyliferous duct'', and ''Van Hoorne's canal''. The other duct is the right ...

s. This happens so that the full repertoire of antigenic specificities of lymphocytes is continuously represented throughout the body. Homing happens in tissue-specific manner—e.g.

B lymphocytes B cells, also known as B lymphocytes, are a type of white blood cell of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system. B cells produce antibody molecules which may be either secreted or ...

migrate better to mucosa-associated lymphoid tissue (

Peyer's patches Peyer's patches (or aggregated lymphoid nodules) are organized lymphoid follicles, named after the 17th-century Swiss anatomist Johann Conrad Peyer. * Reprinted as: * Peyer referred to Peyer's patches as ''plexus'' or ''agmina glandularum'' (clu ...

), and

T lymphocytes A T cell is a type of lymphocyte. T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell rec ...

preferentially to the peripheral

lymph nodes A lymph node, or lymph gland, is a kidney-shaped organ of the lymphatic system and the adaptive immune system. A large number of lymph nodes are linked throughout the body by the lymphatic vessels. They are major sites of lymphocytes that includ ...

. The process of lymphocyte homing is deliberate, mediated by lymphocyte-endothelial recognition mechanisms that enable antigen-specific immune responses. Lymphocyte homing receptor control of organ-specific lymphocyte trafficking is thought to prevent autoreactivity in immune responses during B and T cell differentiation. Recently, lymphocyte homing has become a topic of interest for investigation of treatments for

multiple sclerosis Multiple (cerebral) sclerosis (MS), also known as encephalomyelitis disseminata or disseminated sclerosis, is the most common demyelinating disease, in which the insulating covers of nerve cells in the brain and spinal cord are damaged. This d ...

type 1 diabetes mellitus Type 1 diabetes (T1D), formerly known as juvenile diabetes, is an autoimmune disease that originates when cells that make insulin (beta cells) are destroyed by the immune system. Insulin is a hormone required for the cells to use blood sugar for ...

leukemia Leukemia ( also spelled leukaemia and pronounced ) is a group of blood cancers that usually begin in the bone marrow and result in high numbers of abnormal blood cells. These blood cells are not fully developed and are called ''blasts'' or ' ...

, and

psoriasis Psoriasis is a long-lasting, noncontagious autoimmune disease characterized by raised areas of abnormal skin. These areas are red, pink, or purple, dry, itchy, and scaly. Psoriasis varies in severity from small, localized patches to complete ...

Homing mechanisms

Naive lymphocyte homing

Naive lymphocytes are able to circulate into secondary lymphoid tissues, Peyer’s patches, lymph nodes, and the spleen. Because they have not yet been exposed to antigen, these lymphocytes are undifferentiated and express few homing receptors.

High endothelial venules High endothelial venules (HEV) are specialized post-capillary venous swellings characterized by plump endothelial cells as opposed to the usual thinner endothelial cells found in regular venules. HEVs enable lymphocytes circulating in the blood to ...

(HEVs) are cells found in secondary lymphoid organs that express large quantities of cell adhesion molecules, enabling undifferentiated lymphocytes to bind. After entering lymph nodes and Peyer’s patches via HEVs, naive T and B cells are exposed to antigen circulating in lymph and differentiate to contribute to the

adaptive immune response The adaptive immune system, also known as the acquired immune system, is a subsystem of the immune system that is composed of specialized, systemic cells and processes that eliminate pathogens or prevent their growth. The acquired immune system ...

. HEVs develop from cytokine production after exposure to antigen and express adhesion molecules from the

selectin The selectins (cluster of differentiation 62 or CD62) are a family of cell adhesion molecules (or CAMs). All selectins are single-chain transmembrane glycoproteins that share similar properties to C-type lectins due to a related amino terminus a ...

family,

mucin Mucins () are a family of high molecular weight, heavily glycosylated proteins (glycoconjugates) produced by epithelial tissues in most animals. Mucins' key characteristic is their ability to form gels; therefore they are a key component in most ...

-like family, and the Ig superfamily. Naive lymphocyte

extravasation __NOTOC__ Extravasation is the leakage of a fluid out of its container into the surrounding area, especially blood or blood cells from vessels. In the case of inflammation, it refers to the movement of white blood cells from the capillaries to the ...

into Peyer’s patches is often mediated by

L-selectin L-selectin, also known as CD62L, is a cell adhesion molecule found on the cell surface of leukocytes, and the blastocyst. It is coded for in the human by the ''SELL'' gene. L-selectin belongs to the selectin family of proteins, which recognize s ...

and limited expression of α4 integrins and other homing receptors prevents these lymphocytes from accessing mucosal effector tissue.

Mature lymphocyte homing

Mature lymphocytes are constantly recirculating in the blood and can traffic to secondary lymphoid tissue as well as target tissue including mucosal tissues of the

lamina propria The lamina propria is a thin layer of connective tissue that forms part of the moist linings known as mucous membranes or mucosae, which line various tubes in the body, such as the respiratory tract, the gastrointestinal tract, and the urogenita ...

, inflammation, and other extralymphoid immune effector sites. Lymphocyte homing receptor expression is altered by

antigen exposure In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response. ...

. This function enables the adaptive immune system to specialize an immune response in different parts of the body. Upon exposure to antigens, lymphocytes lack homing ability during a period of

sessile Sessility, or sessile, may refer to: * Sessility (motility), organisms which are not able to move about * Sessility (botany), flowers or leaves that grow directly from the stem or peduncle of a plant * Sessility (medicine), tumors and polyps that ...

differentiation and cell division, and antigen specific lymphocytes are stored in the spleen for 1–3 days. Subsequently, antigen-stimulated B and T cells express homing receptors particularly for the HEV in initial site of immunization tissue. Furthermore, lymphocytes can alter cell adhesion molecule “activatability” to increase binding ability. Organ-specific lymphocyte homing is important for antigen-specificity and in avoiding autoimmune cross-reactions.

Extravasation of lymphocytes

Lymphocyte homing occurs in four steps leading to extravasation into target tissue; Rolling, activation, activation-dependent “arrest”, and

diapedesis Leukocyte extravasation (also commonly known as leukocyte adhesion cascade or diapedesis – the passage of cells through the intact vessel wall) is the movement of leukocytes out of the circulatory system and towards the site of tissue damage or ...

. Mediated by lymphocyte receptors and vascular ligand interactions, “tethering” is a reversible linkage that leads to either rolling along the vessel wall or transient immediate arrest. L-selectin is able to mediate vessel adhesion whereas α4 integrins, α4β1 or α4β7, can perform primary or secondary adhesion through a stronger tethering and even contribute to transendothelial migration of lymphocytes. L-selectin, for example, is also able to be cleaved by an enzyme, ensuring proper binding of lymphocytes and allowing release of non-target cells. While attached to the vessel, lymphocytes test target tissue for

chemokine Chemokines (), or chemotactic cytokines, are a family of small cytokines or signaling proteins secreted by cells that induce directional movement of leukocytes, as well as other cell types, including endothelial and epithelial cells. In additio ...

s and pro-adhesive factors that then prompt “arrest.” In addition to α4 integrins,

LFA-1 Lymphocyte function-associated antigen 1 (LFA-1) is an integrin found on lymphocytes and other leukocytes. LFA-1 plays a key role in emigration, which is the process by which leukocytes leave the bloodstream to enter the tissues. LFA-1 also mediates ...

and Mac-1 mediate the prevention of lymphocyte transendothelial migration into target tissues. While initial adhesion indicates the start of lymphocyte homing, there is regulation of each step of extravasation.

Examples of lymphocyte homing receptors

α4β7 is an α4 integrin class homing receptor that targets lymphocytes in the gut expressing mucosal adhesion molecule-1(

MAdCAM-1 Mucosal vascular addressin cell adhesion molecule 1 (MAdCAM-1) is a protein that in humans is encoded by the ''MADCAM1'' gene. The protein encoded by this gene is an endothelial cell adhesion molecule that interacts preferentially with the leukoc ...

), mostly expressed in Peyer’s patches. Additionally, α4β1 with the ligand vascular adhesion molecule-1(

VCAM-1 Vascular cell adhesion protein 1 also known as vascular cell adhesion molecule 1 (VCAM-1) or cluster of differentiation 106 (CD106) is a protein that in humans is encoded by the ''VCAM1'' gene. VCAM-1 functions as a cell adhesion molecule. Stru ...

) function in lymphocyte trafficking and inflammation. Two other well known examples are

CD34 CD34 is a transmembrane phosphoglycoprotein protein encoded by the CD34 gene in humans, mice, rats and other species. CD34 derives its name from the cluster of differentiation protocol that identifies cell surface antigens. CD34 was first descri ...

and

GLYCAM-1 Glycosylation-dependent cell adhesion molecule-1 (GLYCAM1) is a proteoglycan ligand expressed on cells of the high endothelial venules in lymphoid tissues. It is the ligand for the receptor L-selectin L-selectin, also known as CD62L, is a cell a ...

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B lymphocyte B cells, also known as B lymphocytes, are a type of white blood cell of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system. B cells produce antibody molecules which may be either secreted or ...

T lymphocyte A T cell is a type of lymphocyte. T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell rec ...

References

{{Cell adhesion molecules Cell adhesion molecules