B-Cell Activating Factor

B-Cell Activating Factor

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About B-Cell Activating Factor:

B-Cell Activating factor is a protein, which is encoded by the human TNFSF13B gene. B-Cell Activating Factor, BAFF, is a member of the tumor necrosis family, also known as TNF. This protein is best known for its role in the creation and maintenance of healthy B cells. Excessive production of BAFF is often linked to autoimmune conditions. This page will provide detailed information about BAFF, its functions, interactions, and mechanisms. 

B-Cell Activating Factor aliases

This protein has many aliases, including BLyS (B-Lymphocyte Stimulator), BAFF, tumor necrosis factor ligand superfamily member 13B, TALL1 (TNF-and APOL-related leukocyte expressed ligand) and Dendritic cell-derived TNF-like molecule (also known as CD257 antigen). 

An introduction to BAFF

BAFF, B-Cell Activating Factor, is a member of the TNF (tumor necrosis family) of proteins. BAFF is often linked to autoimmune conditions, but this relates to an overproduction of B-Cell Activating Factor. At a normal level, BAFF plays an instrumental role in protecting and maintaining the body’s immune system. BAFF is known as an immunostimulant, and it is vital for the activation of B-cells. If levels of BAFF are too low, this could contribute to immunodeficiency. If levels are excessive, there is a high risk of autoimmune disease.
B-Cell Activating Factor is a cytokine. Cytokines are substances, which affect other cells. They are secreted by cells that are part of the immune system. BAFF is a cytokine that belongs to the tumor necrosis family of ligands. This particular protein is a molecule that bonds to receptors including TNFRSF13B/TAC1, TNFRSF17/BCMA, and TNFSRF13C/BAFF-R; these receptors are also known as BAFF-R, TACI (transmembrane activator and calcium modulator) and BCMA (B-Cell maturation Ag). 

The structure of BAFF

BAFF is a peptide glycoprotein, which comprises a chain of 285 amino acids. This amino acid chain undergoes a chemical process known as glycosylation, which contributes to the production of type II transmembrane protein by multiple cells. BAFF is produced by a broad spectrum of cells, including:

Dendritic cells
Bone marrow cells
Cells in the spleen and lymph nodes

It is possible to convert the transmembrane protein into a soluble protein. The concentration of BAFF is dependent on the production of receptors that bind with BAFF, including BAFF-R, TACI, and BCMA. The different receptors have varying levels of affinity with BAFF; TACI has the lowest affinity as it prefers to bond with a similar protein known as APRIL. BAFF-R is the dominant receptor in the expression of B cells. Studies show that in both humans and mice, other receptors have a much more limited pattern of expression. As well as being a stimulant for B cell production, BAFF also plays a part in T cell production. 

What does B-Cell Activating factor do?

B-Cell Activating Factor is most commonly known for its role in the growth, development, and survival of B-cells. B cells are a type of white blood cell and more specifically, a form of lymphocyte. B cells develop into plasma cells that produce antibodies or memory cells known as memory B cells. Antibodies are proteins, which are used by the body to detect and fight infections and illnesses. Plasma B cells play an important role in producing antibodies, which target antigens as part of the immune response. Memory cells are designed to remember threats to enable the body to act quickly if the same antigen is detected.
B cells are produced in the liver during gestation and then the bone marrow from weeks 14-17 of pregnancy.
B-Cell Activating Factor is a powerful B cell activator, and it also plays a role in the long-term survival of resting B cells.
In addition to its role in the production and survival of B cells, BAFF is also linked to T cell production. T cells are a type of lymphocyte, which are predominantly fabricated in the thymus. The role of a T cell is to detect antigens. There are two main types of T cell: the cytotoxic T cell and the helper T cell. Cytotoxic T cells are designed to kill harmful cells and tumors, while helper cells help other components of the immune system to fight illness. 

BAFF is clinically significant for its role in maintaining immunity and enabling the human body to fight illness. Although the production of BAFF is essential for ensuring an effective immune response, regulation is of paramount importance, as high levels of BAFF can increase the risk of autoimmune conditions and underproduction of BAFF can lead to immunodeficiency, which occurs as a result of failing to stimulate B cells to produce sufficient levels of immunoglobulin. Autoimmune diseases that are linked to excessive production of BAFF and the overproduction of antibodies include systemic lupus erythematosus (SLE), Sjogren’s syndrome and rheumatoid arthritis. Increased levels of BAFF have also been identified as a risk factor for transplant failure with researchers detecting elevated levels following the rejection of donor organs and allografts. 

BAFF interactions
B-Cell Activating Factor is known to interact with TNFRSF13B (transmembrane activator and CAML interactor or TACI), TNFSF13 (a proliferation-inducing ligand or APRIL) and TNFRSF17 (B-cell maturation antigen or BCMA). The interaction between BAFF and BAFF-R provides essential information, which triggers the production and maintenance of B cells and is consequently critical for B cell survival. 

The recombinant production of BAFF
Human BLyS/BAFF/TNFSF13B is expressed from an E.Coli host and purified. It remains active after the purification process and samples may contain up to half of the bacteria’s original protein content. 

Autoimmune disease and BAFF
Elevated levels of BAFF have been linked to a host of different autoimmune conditions. These diseases include: 

SLE (systemic lupus erythematosus)
Systemic lupus erythematosus, more commonly known as lupus, is an autoimmune condition that can affect several parts of the body. SLE is a severe form of lupus, which can cause a range of different symptoms, including inflammation and pain in the joints, skin rashes and fatigue. It is common for people who suffer from lupus to experience prolonged periods of no symptoms, which are interrupted by flare-ups that cause severe symptoms. Lupus is most commonly diagnosed in women aged between 18 and 50. Treatment options for lupus include medications that are designed to alleviate symptoms, for example, swelling and joint pain, and suppress the actions of the immune system. Immunosuppressants reduce the efficacy of the immune system, preventing antibodies from attacking healthy cells. In the case of lupus, there have been major developments in the production of antibodies that inhibit the actions of B-lymphocyte stimulator or BLyS. Clinical trials of Belimumab (also known as Benlysta) have paved the way for new treatments for lupus and other autoimmune conditions, including rheumatoid arthritis. Belimumab was the first new drug approved by the US Food and Drug Administration for the treatment of SLE in more than 50 years. The drug works by binding to BAFF and neutralizing its impact. 

Sjogren’s Syndrome
Sjogren’s syndrome is an autoimmune disease that affects parts of the body that produce fluid. It is most common in people aged between 40 and 60 years old and the majority of cases are found in females. The most common symptoms of Sjogren’s syndrome are dry eyes, dry mouth, fatigue, dry skin, joint and muscle pain, skin rashes, particularly after sun exposure, and swelling in the salivary glands. It is possible for Sjogren’s syndrome to occur alongside other autoimmune conditions, including lupus and rheumatoid arthritis. In this case, the disease is known as secondary Sjogren’s syndrome. Autoimmune conditions occur when the body starts to attack and destroy healthy tissue, in this case, the epithelial tissue, as part of an immune response. The body mistakenly detects a threat, and the response is triggered. In people with Sjogren’s syndrome, the B cell plays an instrumental role, and it is therefore unsurprising that B-Cell Activating Factor is often linked to Sjogren’s syndrome. The overproduction of BAFF causes abnormal distribution and activity of B cells, break down of B cell tolerance and the creation of autoantibodies. 

Belimumab is sometimes recommended as a treatment for Sjogren’s syndrome in cases where symptoms are more severe, and other treatments have proven ineffective. According to studies, treatment with Belimumab leads to reduction in disease scores and the levels of abnormal B cells. There is also evidence to suggest that this form of medication can ease symptoms such as joint pain and inflammation and fatigue, although it has little impact on dryness in the eyes and mouth. If patients do suffer from a dry mouth or dry eyes, eye drops, ointments, and oral sprays are widely available. 

Rheumatoid arthritis
Rheumatoid arthritis (RA) is an autoimmune condition that affects the joints. The most common symptoms of RA are swollen, painful joints. In most cases, pain is symmetrical, meaning that both sides of the body are affected equally. It is common for symptoms to develop in the hands and feet before other parts of the body. Most people report a throbbing pain and persistent aches. In addition to pain, rheumatoid arthritis can also cause stiffness and a restricted range of motion in the joints and inflammation, which causes the joints to become warm. Some people also experience redness in the skin as a result of the formation of rheumatoid nodules underneath the surface of the skin. If you suffer from RA, you may also be susceptible to tiredness, excessive sweating, weight loss and changes in your appetite. 
Rheumatoid arthritis causes the body to attack the healthy cells in the lining of the joints, known as the synovium. This causes the body to release chemicals, which damage the cartilage, tendons and bones. Elevated levels of B-Cell Activating Factor have been identified in patients with rheumatoid arthritis, and the levels of BAFF are known to correlate with disease activity. Research confirms that overproduction of BAFF and its receptors is linked to developments in RA and interactions that take place between different cell types.

There are various treatment options for rheumatoid arthritis, including medications that are designed to suppress the immune system, including BAFF antagonists. 

Additional clinical effects of elevated BAFF levels 
Food intolerance and inflammation
There is evidence to suggest that excessive levels of BAFF may be associated with inflammation linked to food intolerances and allergies. Studies show that elevated levels of BAFF can be found in people who have inflammation not linked to allergies (non-atopic). Previously, research has been carried out on the role of BAFF in patients with inflammatory bowel disease, as the protein is produced in the mucosa cells within the bowel. Analysis suggests that following a gluten-free diet reduces BAFF levels in celiac sufferers. 

Obesity and diabetes
In cases where there is a link between inflammation and obesity or type 2 diabetes, BAFF has been found to exert a significant influence. BAFF can contribute to insulin resistance, and there is a theory that it raises signals that encourage the body to start storing fat to prevent weight loss and starvation. 

BAFF and asthma
Studies have shown that levels of B-Cell Activating Factor are higher in asthmatic children than children who do not suffer from asthma. Analysis and evaluation of sputum samples suggest that BAFF may play a role in increasing the risk of childhood asthma. Furthermore, there is evidence to suggest that the extent of overproduction may be linked to the severity of symptoms. 

In summary
B-Cell Activating Factor, also known as BAFF, TNFSF13B, BLyS, TNF superfamily member 13 and tumour necrosis factor superfamily member 13, is a protein, which has an instrumental role in stimulating the production of B cells. B cells are lymphocytes, which are part of the white blood cell family. BAFF activates B cells, and it also plays an important role in the development and survival of these cells. If levels of BAFF are too low, this could contribute to a shortage of immunoglobulin and consequently lead to immunodeficiency. If levels are elevated, there is a risk of autoimmune disease. Autoimmune diseases occur when the body attacks healthy tissue mistaking it for a harmful threat; examples include SLE (systemic lupus erythematosus), rheumatoid arthritis and Sjogren’s syndrome.