A lymphocyte is one of the subtypes of a white blood cell in a vertebrate's immune system. Lymphocytes include natural killer cells (which function in cell-mediated, cytotoxic innate immunity), T cells (for cell-mediated, cytotoxic adaptive immunity), and B cells (for humoral, antibody-driven adaptive immunity). They are the main type of cell found in lymph, which prompted the name "lymphocyte".
A scanning electron microscope (SEM) image of a single human lymphocyte.
|Function||White blood cell|
|Anatomical terms of microanatomy|
T cells (thymus cells) and B cells (bone marrow- or bursa-derived cells[a]) are the major cellular components of the adaptive immune response. T cells are involved in cell-mediated immunity, whereas B cells are primarily responsible for humoral immunity (relating to antibodies). The function of T cells and B cells is to recognize specific "non-self" antigens, during a process known as antigen presentation. Once they have identified an invader, the cells generate specific responses that are tailored to maximally eliminate specific pathogens or pathogen-infected cells. B cells respond to pathogens by producing large quantities of antibodies which then neutralize foreign objects like bacteria and viruses. In response to pathogens some T cells, called T helper cells, produce cytokines that direct the immune response, while other T cells, called cytotoxic T cells, produce toxic granules that contain powerful enzymes which induce the death of pathogen-infected cells. Following activation, B cells and T cells leave a lasting legacy of the antigens they have encountered, in the form of memory cells. Throughout the lifetime of an animal, these memory cells will "remember" each specific pathogen encountered, and are able to mount a strong and rapid response if the same pathogen is detected again; this is known as acquired immunity.
NK cells are a part of the innate immune system and play a major role in defending the host from tumors and virally infected cells. NK cells distinguish infected cells and tumors from normal and uninfected cells by recognizing changes of a surface molecule called MHC (major histocompatibility complex) class I. NK cells are activated in response to a family of cytokines called interferons. Activated NK cells release cytotoxic (cell-killing) granules which then destroy the altered cells. They are named "natural killer cells" because they do not require prior activation in order to kill cells which are missing MHC class I.
Mammalian stem cells differentiate into several kinds of blood cell within the bone marrow. This process is called haematopoiesis. All lymphocytes originate, during this process, from a common lymphoid progenitor before differentiating into their distinct lymphocyte types. The differentiation of lymphocytes follows various pathways in a hierarchical fashion as well as in a more plastic fashion. The formation of lymphocytes is known as lymphopoiesis. B cells mature into B lymphocytes in the bursa equivalent, which in humans is the GALT, which is thought to be located in the Peyer's patches of the intestine, while T cells migrate to and mature in a distinct organ, called the thymus. Following maturation, the lymphocytes enter the circulation and peripheral lymphoid organs (e.g. the spleen and lymph nodes) where they survey for invading pathogens and/or tumor cells.
The lymphocytes involved in adaptive immunity (i.e. B and T cells) differentiate further after exposure to an antigen; they form effector and memory lymphocytes. Effector lymphocytes function to eliminate the antigen, either by releasing antibodies (in the case of B cells), cytotoxic granules (cytotoxic T cells) or by signaling to other cells of the immune system (helper T cells). Memory T cells remain in the peripheral tissues and circulation for an extended time ready to respond to the same antigen upon future exposure; they live weeks to several years, which is very long compared to other leukocytes.
Microscopically, in a Wright's stained peripheral blood smear, a normal lymphocyte has a large, dark-staining nucleus with little to no eosinophilic cytoplasm. In normal situations, the coarse, dense nucleus of a lymphocyte is approximately the size of a red blood cell (about 7 μm in diameter). Some lymphocytes show a clear perinuclear zone (or halo) around the nucleus or could exhibit a small clear zone to one side of the nucleus. Polyribosomes are a prominent feature in the lymphocytes and can be viewed with an electron microscope. The ribosomes are involved in protein synthesis, allowing the generation of large quantities of cytokines and immunoglobulins by these cells.
It is impossible to distinguish between T cells and B cells in a peripheral blood smear. Normally, flow cytometry testing is used for specific lymphocyte population counts. This can be used to determine the percentage of lymphocytes that contain a particular combination of specific cell surface proteins, such as immunoglobulins or cluster of differentiation (CD) markers or that produce particular proteins (for example, cytokines using intracellular cytokine staining (ICCS)). In order to study the function of a lymphocyte by virtue of the proteins it generates, other scientific techniques like the ELISPOT or secretion assay techniques can be used.
|Class||Function||Proportion (median, 95% CI)||Phenotypic marker(s)|
|Natural killer cells||Lysis of virally infected cells and tumour cells||7% (2–13%)||CD16 CD56 but not CD3|
|T helper cells||Release cytokines and growth factors that regulate other immune cells||46% (28–59%)||TCRαβ, CD3 and CD4|
|Cytotoxic T cells||Lysis of virally infected cells, tumour cells and allografts||19% (13–32%)||TCRαβ, CD3 and CD8|
|Gamma delta T cells||Immunoregulation and cytotoxicity||5% (2–8%)||TCRγδ and CD3|
|B cells||Secretion of antibodies||23% (18–47%)||MHC class II, CD19 and CD20|
A lymphocyte count is usually part of a peripheral complete blood cell count and is expressed as the percentage of lymphocytes to the total number of white blood cells counted.
An increase in lymphocyte concentration is usually a sign of a viral infection (in some rare case, leukemias are found through an abnormally raised lymphocyte count in an otherwise normal person). A high lymphocyte count with a low neutrophil count might be caused by lymphoma. Pertussis toxin (PTx) of Bordetella pertussis, formerly known as lymphocytosis-promoting factor, causes a decrease in the entry of lymphocytes into lymph nodes, which can lead to a condition known as lymphocytosis, with a complete lymphocyte count of over 4000 per μl in adults or over 8000 per μl in children. This is unique in that many bacterial infections illustrate neutrophil-predominance instead.
A low normal to low absolute lymphocyte concentration is associated with increased rates of infection after surgery or trauma.
One basis for low T cell lymphocytes occurs when the human immunodeficiency virus (HIV) infects and destroys T cells (specifically, the CD4+ subgroup of T lymphocytes). Without the key defense that these T cells provide, the body becomes susceptible to opportunistic infections that otherwise would not affect healthy people. The extent of HIV progression is typically determined by measuring the percentage of CD4+ T cells in the patient's blood – HIV ultimately progresses to acquired immune deficiency syndrome (AIDS). The effects of other viruses or lymphocyte disorders can also often be estimated by counting the numbers of lymphocytes present in the blood.
Anti-lymphocyte globulin (ALG) is an infusion of animal- antibodies against human T cells which is used in the treatment of acute rejection in organ transplantation. Its use was first reported by Thomas Starzl in 1966. Its use in transplant was supplanted by thymoglobulin between 1984 and 1999.It has also been used in the treatment of aplastic anemia.It is less commonly used than the similar anti-thymocyte globulin (ATG), and like ATG it is associated with cytokine release syndrome in the short term and an increased risk of post-transplant lymphoproliferative disorder in the long term. ALG is more likely to cause side effects than ATG, but is safer than OKT3.
The product was manufactured by Upjohn and Merieux, as well as the Schweizerisches Serum- und Impfinstitut in Bern, the latter of which was made by injecting horses with human thoracic duct lymphocytes and was called "Lymphoser Berna".B-cell activating factor
B-cell activating factor (BAFF) also known as tumor necrosis factor ligand superfamily member 13B is a protein that in humans is encoded by the TNFSF13B gene. BAFF is also known as B Lymphocyte Stimulator (BLyS) and TNF- and APOL-related leukocyte expressed ligand (TALL-1) and the Dendritic cell-derived TNF-like molecule (CD257 antigen; cluster of differentiation 257).BTLA
B- and T-lymphocyte attenuator is a protein that in humans is encoded by the BTLA gene. BTLA has also been designated as CD272 (cluster of differentiation 272).B cell
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 by secreting antibodies. Additionally, B cells present antigen (they are also classified as professional antigen-presenting cells (APCs)) and secrete cytokines.
In mammals, B cells mature in the bone marrow, which is at the core of most bones. In birds, B cells mature in the bursa of Fabricius, a lymphoid organ. (The "B" from B cells comes from the name of this organ, where it was first discovered by Chang and Glick, and not from bone marrow as commonly believed).
B cells, unlike the other two classes of lymphocytes, T cells and natural killer cells, express B cell receptors (BCRs) on their cell membrane. BCRs allow the B cell to bind to a specific antigen, against which it will initiate an antibody response.Bare lymphocyte syndrome
Bare lymphocyte syndrome is a condition caused by mutations in certain genes of the major histocompatibility complex or involved with the processing and presentation of MHC molecules. It is a form of severe combined immunodeficiency.CTLA-4
CTLA4 or CTLA-4 (cytotoxic T-lymphocyte-associated protein 4), also known as CD152 (cluster of differentiation 152), is a protein receptor that functions as an immune checkpoint and downregulates immune responses. CTLA4 is constitutively expressed in regulatory T cells but only upregulated in conventional T cells after activation – a phenomenon which is particularly notable in cancers. It acts as an "off" switch when bound to CD80 or CD86 on the surface of antigen-presenting cells.
The CTLA-4 protein is encoded by the Ctla4 gene in mice and the CTLA4 gene in humans.Cytotoxic T cell
A cytotoxic T cell (also known as TC, cytotoxic T lymphocyte, CTL, T-killer cell, cytolytic T cell, CD8+ T-cell or killer T cell) is a T lymphocyte (a type of white blood cell) that kills cancer cells, cells that are infected (particularly with viruses), or cells that are damaged in other ways.
Most cytotoxic T cells express T-cell receptors (TCRs) that can recognize a specific antigen. An antigen is a molecule capable of stimulating an immune response, and is often produced by cancer cells or viruses. Antigens inside a cell are bound to class I MHC molecules, and brought to the surface of the cell by the class I MHC molecule, where they can be recognized by the T cell. If the TCR is specific for that antigen, it binds to the complex of the class I MHC molecule and the antigen, and the T cell destroys the cell.
In order for the TCR to bind to the class I MHC molecule, the former must be accompanied by a glycoprotein called CD8, which binds to the constant portion of the class I MHC molecule. Therefore, these T cells are called CD8+ T cells.
The affinity between CD8 and the MHC molecule keeps the TC cell and the target cell bound closely together during antigen-specific activation. CD8+ T cells are recognized as TC cells once they become activated and are generally classified as having a pre-defined cytotoxic role within the immune system. However, CD8+ T cells also have the ability to make some cytokines.Hodgkin's lymphoma
Hodgkin's lymphoma (HL) is a type of lymphoma in which cancer originates from a specific type of white blood cells called lymphocytes. Symptoms may include fever, night sweats, and weight loss. Often there will be non-painful enlarged lymph nodes in the neck, under the arm, or in the groin. Those affected may feel tired or be itchy.About half of cases of Hodgkin's lymphoma are due to Epstein–Barr virus (EBV). Other risk factors include a family history of the condition and having HIV/AIDS. There are two major types of Hodgkin lymphoma: classical Hodgkin lymphoma and nodular lymphocyte-predominant Hodgkin lymphoma. Diagnosis is by finding Hodgkin's cells such as multinucleated Reed–Sternberg cells (RS cells) in lymph nodes. The virus-positive cases are classified as a form of the Epstein-Barr virus-associated lymphoproliferative diseases.Hodgkin lymphoma may be treated with chemotherapy, radiation therapy, and stem cell transplant. The choice of treatment often depends on how advanced the cancer has become and whether or not it has favorable features. In early disease, a cure is often possible. The percentage of people who survive five years in the United States is 86%. For those under the age of 20, rates of survival are 97%. Radiation and some chemotherapy drugs, however, increase the risk of other cancers, heart disease, or lung disease over the subsequent decades.In 2015, about 574,000 people had Hodgkin's lymphoma, and 23,900 died. In the United States, 0.2% of people are affected at some point in their life. The most common age of diagnosis is between 20 and 40 years old. It was named after the English physician Thomas Hodgkin, who first described the condition in 1832.L-selectin
L-selectin, also known as CD62L, is a cell adhesion molecule found on leukocytes and the preimplantation embryo. It belongs to the selectin family of proteins, which recognize sialylated carbohydrate groups. It is cleaved by ADAM17.
SELL is a cell surface component that is a member of a family of adhesion/homing receptors that play important roles in lymphocyte-endothelial cell interactions. The molecule is composed of multiple domains: one homologous to lectins, one to epidermal growth factor, and two to the consensus repeat units found in C3/C4-binding proteins.LAG3
Lymphocyte-activation gene 3, also known as LAG-3, is a protein which in humans is encoded by the LAG3 gene. LAG3, which was discovered in 1990 and was designated CD223 (cluster of differentiation 223) after the Seventh Human Leucocyte Differentiation Antigen Workshop in 2000, is a cell surface molecule with diverse biologic effects on T cell function. It is an immune checkpoint receptor and as such is the target of various drug development programs by pharmaceutical companies seeking to develop new treatments for cancer and autoimmune disorders. In soluble form it is also being developed as a cancer drug in its own right.Lck
Lck (or lymphocyte-specific protein tyrosine kinase) is a 56 kDa protein that is found inside specialized cells of the immune system called lymphocytes. Lck is a tyrosine kinase, which phosphorylates tyrosine residues of certain proteins involved in the intracellular signaling pathways of these lymphocytes. It is a member of the Src family of tyrosine kinases.Lymphoblast
A lymphoblast is a modified naive lymphocyte with altered cell morphology. It occurs when the lymphocyte is activated by an antigen (from antigen-presenting cells) and increased in volume by nucleus and cytoplasm growth as well as new mRNA and protein synthesis. The lymphoblast then starts dividing two to four times every 24-hours for 3-5 days, with a single lymphoblast making approximately 1000 clones of its original naive lymphocyte, with each sharing the originally unique antigen specificity. Finally the dividing cells differentiate into effector cells, known as Plasma Cells (for B cells), Cytotoxic T cells, and Helper T cells.Lymphoblasts can also refer to immature cells which typically differentiate to form mature lymphocytes. Normally lymphoblasts are found in the bone marrow, but in acute lymphoblastic leukemia (ALL), lymphoblasts proliferate uncontrollably and are found in large numbers in the peripheral blood.
The size is between 10 and 20 μm.Although commonly lymphoblast refers to a precursor cell in the maturation of leukocytes, the usage of this term is sometimes inconsistent. The Chronic Lymphocytic Leukemia Research Consortium defines a lymphoblast as "A lymphocyte that has become larger after being stimulated by an antigen. Lymphoblasts look like immature lymphocytes, and were once thought to be precursor cells.". Commonly, when speaking about leukemia, "blast" is used as an abbreviation for lymphoblasts.
Lymphoblasts can be distinguished microscopically from myeloblasts by having less distinct nucleoli, more condensed chromatin, and an absence of cytoplasmic granules. However these morphologic distinctions are not absolute and a definitive diagnoses relies on antibody immunostaining for the presence of unique cluster of differentiation receptors.Lymphocyte function-associated antigen 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 firm arrest of leukocytes. Additionally, LFA-1 is involved in the process of cytotoxic T cell mediated killing as well as antibody mediated killing by granulocytes and monocytes. As of 2007, LFA-1 has 6 known ligands: ICAM-1, ICAM-2, ICAM-3, ICAM-4, ICAM-5, and JAM-A. LFA-1/ICAM-1 interactions have recently been shown to stimulate signaling pathways that influence T cell differentiation. LFA-1 belongs to the integrin superfamily of adhesion molecules.Natural killer cell
Natural killer cells, or NK cells, are a type of cytotoxic lymphocyte critical to the innate immune system. The role NK cells play is analogous to that of cytotoxic T cells in the vertebrate adaptive immune response. NK cells provide rapid responses to virus-infected cells, acting at around 3 days after infection, and respond to tumor formation. Typically, immune cells detect major histocompatibility complex (MHC) presented on infected cell surfaces, triggering cytokine release, causing lysis or apoptosis. NK cells are unique, however, as they have the ability to recognize stressed cells in the absence of antibodies and MHC, allowing for a much faster immune reaction. They were named "natural killers" because of the initial notion that they do not require activation to kill cells that are missing "self" markers of MHC class 1. This role is especially important because harmful cells that are missing MHC I markers cannot be detected and destroyed by other immune cells, such as T lymphocyte cells.
NK cells (belonging to the group of innate lymphoid cells) are defined as large granular lymphocytes (LGL) and constitute the third kind of cells differentiated from the common lymphoid progenitor-generating B and T lymphocytes. NK cells are known to differentiate and mature in the bone marrow, lymph nodes, spleen, tonsils, and thymus, where they then enter into the circulation. NK cells differ from natural killer T cells (NKTs) phenotypically, by origin and by respective effector functions; often, NKT cell activity promotes NK cell activity by secreting interferon gamma. In contrast to NKT cells, NK cells do not express T-cell antigen receptors (TCR) or pan T marker CD3 or surface immunoglobulins (Ig) B cell receptors, but they usually express the surface markers CD16 (FcγRIII) and CD56 in humans, NK1.1 or NK1.2 in C57BL/6 mice. The NKp46 cell surface marker constitutes, at the moment, another NK cell marker of preference being expressed in both humans, several strains of mice (including BALB/c mice) and in three common monkey species.In addition to the knowledge that natural killer cells are effectors of innate immunity, recent research has uncovered information on both activating and inhibitory NK cell receptors which play important functional roles, including self tolerance and the sustaining of NK cell activity. NK cells also play a role in the adaptive immune response: numerous experiments have demonstrated their ability to readily adjust to the immediate environment and formulate antigen-specific immunological memory, fundamental for responding to secondary infections with the same antigen. The role of NK cells in both the innate and adaptive immune responses is becoming increasingly important in research using NK cell activity as a potential cancer therapy.Nodular lymphocyte predominant Hodgkin's lymphoma
Nodular lymphocyte predominant Hodgkin's lymphoma (NLPHL) is an indolent CD20(+) form of lymphoma.Some people no longer classified it as a form of classic Hodgkin's lymphoma (HL). This is because the Reed-Sternberg cell (RSC) variants (popcorn cells) that characterize this form of the disease invariably express B lymphocyte markers such as CD20 (thus making NLPHL an unusual form of Hodgkin's lymphoma), and that (unlike classic HL) NLPHL may progress to diffuse large B cell lymphoma.
There are small but clear differences in prognosis between the various forms. Lymphocyte predominant HL is an uncommon subtype composed of vague nodules of numerous reactive lymphocytes admixed with large popcorn-shaped RSC. Unlike classic RSC, the non-classic popcorn-shaped RS cells of NLPHL are CD15 and CD30 negative while positive for the B cell marker CD20. The anti-CD20 monoclonal antibody Rituximab has been used in lymphocyte predominant Hodgkin's lymphoma with encouraging results.BCL6 gene rearrangements have been frequently observed.Peripheral blood lymphocyte
Peripheral blood lymphocytes (PBL) are mature lymphocytes that circulate in the blood, rather than localising to organs (such as the spleen or lymph nodes). They comprise T cells, NK cells and B cells.Reactive lymphocyte
Reactive lymphocytes or variant lymphocytes are cytotoxic (CD8+) lymphocytes that become large as a result of antigen stimulation. Typically, they can be more than 30 µm in diameter with varying size and shape.
The nucleus of a reactive lymphocyte can be round, elliptic, indented, cleft, or folded. The cytoplasm is often abundant and can be basophilic. Vacuoles and/or azurophilic granules are also sometimes present. Most often, the cytoplasm is gray, pale blue, or deep blue in colour.
The distinctive cell associated with EBV or CMV is known as a "Downey cell", after Hal Downey, who contributed to the characterization of it in 1923.T cell
A T cell is a type of lymphocyte which develops in the thymus gland and plays a central role in the immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell receptor on the cell surface. These immune cells originate as precursor cells, derived from bone marrow, and develop into several distinct types of T cells once they have migrated in to the thymus gland - for which these cells are named. T cell differentiation continues even after they have left the thymus.
Groups of specific, differentiated T cells have an important role in controlling and shaping the immune response by providing a variety of immune-related functions. One of these functions is Immune-mediated cell death, and it is carried out by T cells in several ways: CD8+ T cells, also known as "Killer cells", are cytotoxic - this means that they are able to directly kill virus-infected cells as well as cancer cells. CD8+ T cells are also able to utilize small signalling proteins, known as cytokines, to recruit other cells when mounting an immune response. A different population of T cells, the CD4+ T cells, function as "Helper cells". Unlike CD8+ Killer T cells, these CD4+ Helper T cells function by indirectly killing cells identified as foreign: they determine if and how other parts of the immune system responds to a specific, perceived threat. Helper T cells also use cytokine signalling to influence regulatory B cells directly, and other cell populations indirectly. Regulatory T cells are yet another distinct population of these cells that provide the critical mechanism of tolerance, whereby immune cells are able to distinguish invading cells from "self" - thus preventing immune cells from inappropriately mounting a response against oneself (which would by definition be an "autoimmune" response). For this reason these regulatory T cells have also been called "Suppressor" T cells. These same self-tolerant cells are co-opted by cancer cells to prevent the recognition of, and an immune response against, tumour cells.T helper cell
The T helper cells (Th cells), also known as CD4+ cells, are a type of T cell that play an important role in the immune system, particularly in the adaptive immune system. They help the activity of other immune cells by releasing T cell cytokines. These cells help suppress or regulate immune responses. They are essential in B cell antibody class switching, in the activation and growth of cytotoxic T cells, and in maximizing bactericidal activity of phagocytes such as macrophages.
Mature Th cells express the surface protein CD4 and are referred to as CD4+ T cells. Such CD4+ T cells are generally treated as having a pre-defined role as helper T cells within the immune system. For example, when an antigen-presenting cell expresses an antigen on MHC class II, a CD4+ cell will aid those cells through a combination of cell to cell interactions (e.g. CD40 (protein) and CD40L) and through cytokines.
CD154, also called CD40 ligand or CD40L, is a cell surface protein that mediates T cell helper function in a contact-dependent process and is a member of the TNF superfamily of molecules. It binds to CD40 on antigen-presenting cells (APC), which leads to many effects depending on the target cell type. CD154 acts as a costimulatory molecule and is particularly important on a subset of T cells called T follicular helper cells (TFH cells). On TFH cells, CD154 promotes B cell maturation and function by engaging CD40 on the B cell surface and therefore facilitating cell-cell communication. A defect in this gene results in an inability to undergo immunoglobulin class switching and is associated with hyper IgM syndrome. Absence of CD154 also stops the formation of germinal centers and therefore prohibiting antibody affinity maturation, an important process in the adaptive immune system.
The importance of helper T cells can be seen from HIV, a virus that primarily infects CD4+ T cells. In the advanced stages of HIV infection, loss of functional CD4+ T cells leads to the symptomatic stage of infection known as the acquired immunodeficiency syndrome (AIDS). When the HIV virus is detected early in blood or other bodily fluids, continuous therapy can delay the time at which this fall happens. Therapy can also better manage the course of AIDS if and when it occurs. There are other rare disorders such as lymphocytopenia which result in the absence or dysfunction of CD4+ T cells. These disorders produce similar symptoms, many of which are fatal.