B Cells definition
B cells, also known as B lymphocytes, are a type of white blood cell that plays a crucial role in the adaptive humoral immune system. They develop from stem cells in the bone marrow and produce antibodies that bind to pathogens and other foreign substances.
B cells are responsible for mediating the production of antigen-specific immunoglobulin (Ig) and are key players in humoral immunity.
What are B-cells (B lymphocytes)?
B cells, also known as B lymphocytes, are a type of white blood cell that is part of the immune system. They develop from stem cells in the bone marrow. B cells produce antibodies that are used to attack invading bacteria, viruses, and toxins.
When a pathogen enters the body, it is recognized by the B cell’s membrane-bound receptor (BCR) along with accessory cell surface receptors. The B cell then differentiates into plasma cells that secrete large amounts of antibodies specific to the pathogen.
B cells play a critical role in humoral immunity, which is one of two types of adaptive immunity. Humoral immunity involves the production of antibodies that circulate in bodily fluids and can neutralize pathogens before they enter cells.
There are several types of B cells including plasmablasts, plasma cells, and follicular (FO) B cells. FO B cells are the most common type of B cell and are found mainly in lymphoid follicles where they interact with T helper cells to produce high-affinity antibodies.
B cells are white blood cells that produce antibodies to fight off invading pathogens. They play a critical role in humoral immunity and differentiate into plasma cells when activated by a pathogen.
What are the different types of B-cells?
There are four main types of B cells:
- Transitional B cells.
- Naïve B cells.
- Plasma B cells.
- Memory B cells.
1. Transitional B cells
Transitional B cells are a type of B cell that is at an intermediate stage in their development between bone marrow immature cells and mature B cells in the spleen. They represent a crucial link between immature B cells in the bone marrow and mature peripheral B cells.
Transitional B cells are high in heat-stable antigen (HSA, CD24) relative to their mature counterparts and express the phenotypic surface markers AA4.
Although transitional B cells represent one of the regulatory B cell subpopulations in healthy individuals, the frequency of CD24hiCD38hi TrB cells in circulation may be altered in autoimmunity. The data point to the late transitional B-cell stage as a crucial juncture for the negative selection checkpoint for autoreactive B cells.
The term “transitional cell” was first used in 1995 for cells that are developmentally intermediate between immature bone marrow B lineage cells and fully mature naïve B cells in the peripheral blood and secondary lymphoid tissues, found in mice.
In humans, it is postulated that the transitional compartment represents a key negative selection checkpoint for autoreactive B cells.
Transitional B-cells play an important role during human immune system development. They are characterized by their high expression of heat-stable antigen (HSA) relative to their mature counterparts and express phenotypic surface markers AA4.
Transitional B-cells represent one of the regulatory subpopulations of healthy individuals but may be altered during autoimmunity.
2. Naive B cells
Naive B cells are a type of B cell that has not yet encountered an antigen. They circulate through the peripheral blood and lymphatic system, entering secondary lymphoid organs such as the spleen, lymph nodes, tonsils, and Peyer’s patches.
Once exposed to an antigen, naive B cells differentiate into either memory B cells or plasma cells that secrete antibodies specific to the antigen they bound. Memory B cells can last for very long periods of time while plasma cells do not last long in circulation.
Naive B cells are considered ineffective antigen-presenting cells and are unable to activate naive T cells. However, when naive B cells come into contact with a specific antigen, they form germinal centers with the help of CD4 helper T cells. Naive B cells can be activated by direct binding to an antigen.
Once a naive B cell recognizes its target antigen, it forms germinal centers with the help of CD4 helper T cells. Germinal centers are sites within secondary lymphoid organs where activated B cells proliferate and differentiate into memory or plasma cells.
Recent research has shown that naive B cells can generate regulatory T (Treg) cells in the presence of a mature immunologic synapse. Antigen-specific contact between naive B and Treg leads to stable cell pairs that remain associated over hours in vivo. The physiologic role of such pairs has not been evaluated yet.
3. Plasma B cells
Plasma cells are a type of white blood cell that originates in the lymphoid organs as B lymphocytes and play a significant role in the adaptive immune response, being the main cells responsible for humoral immunity. They have differentiated B-lymphocyte white blood cells capable of secreting immunoglobulin or antibodies.
Plasma cells can secrete large amounts of antibodies, making them a key component of humoral immunity. The terminally differentiated or mature plasma cells are non-proliferating, much larger than B cells, and can secrete large amounts of antibodies.
Plasma cells differentiate from B-cells that have been activated. Some B-cells will become plasmablasts (or “immature plasma cells”), and eventually plasma cells, and begin producing large volumes of antibodies.
The most immature blood cell that is considered to be of a plasma cell lineage is the plasmablast. Plasmablasts can proliferate and secrete small amounts of antibodies.
Plasma cells express relatively few surface antigens and do not express common pan-B cell markers such as CD19 and CD20. Instead, they are identified through flow cytometry by their additional expression of CD138, CD78, and the Interleukin-6 receptor.
4. Memory B cells
Memory B cells are a type of B lymphocyte that forms part of the adaptive immune system. They develop within germinal centers of secondary lymphoid organs and circulate in the bloodstream in a quiescent state, sometimes for decades.
Memory B cells are long-lived and quiescent cells that are poised to quickly respond to antigens upon recall.
They are defined as long-lived and quiescent cells that are not described as long-lived plasma cells (LLPCs). Memory B cells can survive for decades, which gives them the capacity to respond to multiple exposures to the same antigen.
Memory B cells provide a second level of protection against re-exposure to pathogens by differentiating into either plasma cells or germinal center (GC) B cells.
The highly-selected, high-affinity antibodies produced by LLPCs form the first line of defense against homologous challenge, while memory B cells provide a second layer of defense against challenges by variant pathogens that escape the first line of defense.
Naive B cells may also give rise to memory B cells in the follicle independently of GCs. In fact, it was shown that BCL-6-deficient mice, which cannot develop GCs, differentiate into both IgM+ and IgG+ memory B cells that had not acquired somatic hypermutation (SHM).
The lifespan of individual memory B cells remains poorly defined, although they have a critical role in long-term immunity.
There is evidence that under steady-state conditions human memory B cells are slowly dividing suggesting that the memory B cell pool may be maintained through homeostatic proliferation as it is the case for memory T-cells.
How do B cells recognize antigens?
B cells recognize antigens through their B-cell antigen receptor (BCR). The BCR is a receptor that recognizes and binds to antigens by the V regions exposed on the surface of the cell, transmitting a signal that causes B-cell activation leading to clonal expansion and specific antibody production.
The immunoglobulins, or Ig, are the antigen-recognition molecules of B cells. These proteins are produced by B cells in a vast range of antigen-specificities.
B cells can recognize and respond to antigens in various forms, but membrane-bound antigens are the predominant forms that initiate B-cell activation.
When infectious agents enter the body, pieces of their machinery can be visible on the surface of their cells. These pieces are called antigens, and B cells activate when they encounter and recognize antigens.
Once the B cells bind to an antigen, they release antibodies that stick to the antigen and prevent it from harming the body. Then, they secrete cytokines to attract other immune cells. They also present the antigens to T cells using their T cell receptors (TCRs), which destroy the antigens.
Follicular dendritic cells (FDCs) play a major role in presenting antigens to B cells and may regulate their selection during affinity maturation.
Larger antigens, including antigens in immune complexes, can be presented to B cells on the surface of other types of cells such as dendritic cells, macrophages, and FDCs. These presenting cells might use a combination of lectin receptors, complement receptors, and/or Fc receptors.
How are B cells activated?
B cells are activated when their receptors recognize an antigen and bind to it. However, in most cases, B-cell activation is dependent on a second factor – stimulation by an activated helper T cell. Once a helper T cell has been activated by an antigen, it becomes capable of activating a B cell that has already encountered the same antigen.
Activation is carried out through a cell-to-cell interaction that occurs between a protein called the CD40 ligand, which appears on the surface of the activated helper T cells, and the CD40 protein on the B-cell surface. The helper T cell also secretes cytokines, which can interact with the B cell and provide additional stimulation.
When naïve or memory B cells are activated by antigen (with the aid of a helper T cell), they proliferate and differentiate into effector cells that make and secrete large amounts of antibodies. Each B cell produces a single species of antibody, each with a unique antigen-binding site.
The first antibodies made by a newly formed B cell are not secreted. Instead, they are inserted into the plasma membrane where they serve as receptors for antigens. Each B cell has approximately 105 such receptors in its plasma membrane.
B-cell activation occurs in secondary lymphoid organs such as the spleen and lymph nodes. Immature B cells migrate from the bone marrow into the spleen as transitional B cells pass through two transitional stages: T1 and T2.
Upon antigenic stimulation, B cells proliferate and form germinal centers where their Ig genes undergo somatic hypermutation and class switch recombination.
The result is a typical thymus-dependent B-cell response with the formation of germinal centers, antibody class switching, affinity maturation, induction of long-lived antibody-secreting plasma cells, and memory B cells.
When an antigen binds to its receptor on a naïve or memory B cell with help from an activated helper T cell in secondary lymphoid organs such as the spleen or lymph nodes; it leads to the proliferation of these cells forming germinal centers where their Ig genes undergo somatic hypermutation and class switch recombination resulting in long-lived antibody-secreting plasma cells and memory B-cells.
How do B-cells work in the immune system?
B-cells, also known as B lymphocytes, are a type of white blood cell that plays an important role in the immune system. They produce proteins called antibodies that help protect the body from harmful pathogens such as viruses and bacteria.
Antibodies are Y-shaped proteins that are specific to each pathogen and can lock onto the surface of an invading cell and mark it for destruction by other immune cells.
When a B-cell encounters an antigen (a foreign substance), it binds to it and divides into plasma cells. These plasma cells then produce large amounts of antibodies that can neutralize or destroy the antigen.
B-cells work with other cells in the immune system to fight harmful invaders that can make you sick and abnormal cells like cancer cells. They also have a positive role in priming adaptive CD4+ T-cells but not CD8+ T-cells.
The adaptive immune system includes both T-cells and B-cells. While the innate immune system is your first defense against any threat, your adaptive immune system is specialized to recognize and fight particular pathogens.
B-cells play a crucial role in protecting the body from harmful pathogens by producing antibodies that can neutralize or destroy them. They work with other cells in the immune system to fight invaders that can make you sick and abnormal cells like cancer cells.
Where are B-cells located?
B cells originate in the bone marrow and mature there in mammals. In birds, B cells mature in the bursa of Fabricius, a lymphoid organ where they were first discovered.
Memory B cells are found not only in the spleen and lymph nodes but also in the bone marrow, Peyers’ patches, gingiva, and mucosal epithelium of tonsils. In fetuses, the liver makes B cells. Once born, B cells continue to develop and mature in the bone marrow.
Why are B-cells important?
B-cells, also known as B lymphocytes, are a type of white blood cell that plays a significant role in protecting the body from infection.
They are responsible for mediating the production of antigen-specific immunoglobulin (Ig), which is an antibody that binds to pathogens or foreign substances to neutralize them.
For example, an antibody can bind to a virus, which prevents it from entering a normal cell and causing infection. B-cells can also recruit other cells to help destroy an infected cell.
B-cells are important because they are part of the adaptive immune system. The adaptive immune system includes both innate and adaptive immunity. While innate immunity is your body’s first line of defense against harmful pathogens, adaptive immunity is more specific and takes longer to develop.
Adaptive immunity involves the recognition of specific antigens by T-cells and B-cells. Once activated, these cells produce antibodies that target the specific antigen.
Without B-cells, the body would not be as effective at fighting off common bacteria and viruses. Additionally, the long-lasting “memory antibody” function that is typical of adaptive immunity would be lacking.
What diseases affect B cells?
B cells play an important role in regulating the immune response in both physiological and pathological conditions. Dysregulation of B-cell function can lead to severe consequences for the host, which are discussed below.
B cells serve as antigen-presenting cells (APCs) in autoimmune diseases such as rheumatoid arthritis and type 1 diabetes.
Recent research has demonstrated that B cells are also involved in the inhibition of inflammatory immune responses, a function carried out by a subpopulation of B cells fittingly named regulatory B cells or Bregs.
Several autoimmune disorders such as multiple sclerosis, N-methyl-d-aspartate receptor (NMDAR) encephalitis, myasthenia gravis, systemic lupus erythematosus (SLE), pemphigus vulgaris, rheumatoid arthritis been treated with B cell depletion therapy (BCDT).
In MS, a complex interplay of neurodegenerative and immunological processes damages the myelin sheaths that surround neurons. There are three clinical variations of MS: relapsing–remitting MS (RRMS), secondary progressive MS (SPMS), and primary progressive MS (PPMS).
Studies have implicated B cells in the pathogenesis of MS. Deposition of complexes containing antibodies and complement components in MS plaques also suggests that B cells are important in MS pathogenesis.
