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 inserted into the plasma membrane where they serve as a part of B-cell receptors. When a naïve or memory B cell is activated by an antigen, it proliferates and differentiates into an antibody-secreting effector cell, known as a plasmablast or plasma cell. In addition, B cells present antigens 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 where they were first discovered by Chang and Glick, which is why the B stands for bursa and not bone marrow, as commonly believed.
Cancer immunotherapy (immuno-oncotherapy) is the stimulation of the immune system to treat cancer, improving the immune system's natural ability to fight the disease. It is an application of the fundamental research of cancer immunology and a growing subspecialty of oncology.
An antigen-presenting cell (APC) or accessory cell is a cell that displays an antigen bound by major histocompatibility complex (MHC) proteins on its surface; this process is known as antigen presentation. T cells may recognize these complexes using their T cell receptors (TCRs). APCs process antigens and present them to T cells.
In immunology, an Fc receptor is a protein found on the surface of certain cells – including, among others, B lymphocytes, follicular dendritic cells, natural killer cells, macrophages, neutrophils, eosinophils, basophils, human platelets, and mast cells – that contribute to the protective functions of the immune system. Its name is derived from its binding specificity for a part of an antibody known as the Fc region. Fc receptors bind to antibodies that are attached to infected cells or invading pathogens. Their activity stimulates phagocytic or cytotoxic cells to destroy microbes, or infected cells by antibody-mediated phagocytosis or antibody-dependent cell-mediated cytotoxicity. Some viruses such as flaviviruses use Fc receptors to help them infect cells, by a mechanism known as antibody-dependent enhancement of infection.
Germinal centers or germinal centres (GCs) are transiently formed structures within B cell zone (follicles) in secondary lymphoid organs – lymph nodes, ileal Peyer's patches, and the spleen – where mature B cells are activated, proliferate, differentiate, and mutate their antibody genes during a normal immune response; most of the germinal center B cells (BGC) are removed by tingible body macrophages. There are several key differences between naive B cells and GC B cells, including level of proliferative activity, size, metabolic activity and energy production. The B cells develop dynamically after the activation of follicular B cells by T-dependent antigen. The initiation of germinal center formation involves the interaction between B and T cells in the interfollicular area of the lymph node, CD40-CD40L ligation, NF-kB signaling and expression of IRF4 and BCL6.
Co-stimulation is a secondary signal which immune cells rely on to activate an immune response in the presence of an antigen-presenting cell. In the case of T cells, two stimuli are required to fully activate their immune response. During the activation of lymphocytes, co-stimulation is often crucial to the development of an effective immune response. Co-stimulation is required in addition to the antigen-specific signal from their antigen receptors.
CD154, also called CD40 ligand or CD40L, is a protein that is primarily expressed on activated T cells 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. In total CD40L has three binding partners: CD40, α5β1 integrin and integrin αIIbβ3. CD154 acts as a costimulatory molecule and is particularly important on a subset of T cells called T follicular helper 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.
Hyper IgM syndrome is a rare primary immune deficiency disorders characterized by low or absent levels of serum IgG, IgA, IgE and normal or increased levels of serum IgM.
The Cluster of differentiation 80 is a B7, type I membrane protein in the immunoglobulin superfamily, with an extracellular immunoglobulin constant-like domain and a variable-like domain required for receptor binding. It is closely related to CD86, another B7 protein (B7-2), and often works in tandem. Both CD80 and CD86 interact with costimulatory receptors CD28, CTLA-4 (CD152) and the p75 neurotrophin receptor.
Tumor necrosis factor receptor superfamily, member 4 (TNFRSF4), also known as CD134 and OX40 receptor, is a member of the TNFR-superfamily of receptors which is not constitutively expressed on resting naïve T cells, unlike CD28. OX40 is a secondary co-stimulatory immune checkpoint molecule, expressed after 24 to 72 hours following activation; its ligand, OX40L, is also not expressed on resting antigen presenting cells, but is following their activation. Expression of OX40 is dependent on full activation of the T cell; without CD28, expression of OX40 is delayed and of fourfold lower levels.
CD16, also known as FcγRIII, is a cluster of differentiation molecule found on the surface of natural killer cells, neutrophils, monocytes, macrophages, and certain T cells. CD16 has been identified as Fc receptors FcγRIIIa (CD16a) and FcγRIIIb (CD16b), which participate in signal transduction. The most well-researched membrane receptor implicated in triggering lysis by NK cells, CD16 is a molecule of the immunoglobulin superfamily (IgSF) involved in antibody-dependent cellular cytotoxicity (ADCC). It can be used to isolate populations of specific immune cells through fluorescent-activated cell sorting (FACS) or magnetic-activated cell sorting, using antibodies directed towards CD16.
CD137, a member of the tumor necrosis factor (TNF) receptor family, is a type 1 transmembrane protein, expressed on surfaces of leukocytes and non-immune cells. Its alternative names are tumor necrosis factor receptor superfamily member 9 (TNFRSF9), 4-1BB, and induced by lymphocyte activation (ILA). It is of interest to immunologists as a co-stimulatory immune checkpoint molecule, and as a potential target in cancer immunotherapy.
OX-2 membrane glycoprotein, also named CD200 is a human protein encoded by the CD200 gene. CD200 gene is in human located on chromosome 3 in proximity to genes encoding other B7 proteins CD80/CD86. In mice CD200 gene is on chromosome 16.
Fc fragment of IgA receptor (FCAR) is a human gene that codes for the transmembrane receptor FcαRI, also known as CD89. FcαRI binds the heavy-chain constant region of Immunoglobulin A (IgA) antibodies. FcαRI is present on the cell surface of myeloid lineage cells, including neutrophils, monocytes, macrophages, and eosinophils, though it is notably absent from intestinal macrophages and does not appear on mast cells. FcαRI plays a role in both pro- and anti-inflammatory responses depending on the state of IgA bound. Inside-out signaling primes FcαRI in order for it to bind its ligand, while outside-in signaling caused by ligand binding depends on FcαRI association with the Fc receptor gamma chain.
The following outline is provided as an overview of and topical guide to immunology:
Hyper-IgM syndrome type 3 is a form of hyper IgM syndrome characterized by mutations of the CD40 gene. In this type, Immature B cells cannot receive signal 2 from helper T cells which is necessary to mature into mature B cells.
Hyper-IgM syndrome type 4 is a form of Hyper IgM syndrome which is a defect in class switch recombination downstream of the AICDA gene that does not impair somatic hypermutation.
Urelumab is a fully human, non‐ligand binding, CD137 agonist immunoglobulin‐γ 4 (IgG4) monoclonal antibody. It was developed utilizing Medarex's UltiMAb(R) technology by Bristol-Myers Squibb for the treatment of cancer and solid tumors. Urelumab promotes anti-tumor immunity, or an immune response against tumor cells, via CD137 activation. The application of Urelumab has been limited due to the fact that it can cause severe liver toxicity.
Immune checkpoints are regulators of the immune system. These pathways are crucial for self-tolerance, which prevents the immune system from attacking cells indiscriminately. However, some cancers can protect themselves from attack by stimulating immune checkpoint targets.
APC Activators are a type of immunotherapy which leverages antigen-presenting cells (APCs) to drive an adaptive immune response. APC Activators are agonists to APC surface-expressed ligands that, when bound, induce the maturation and activation of APCs. Professional antigen-presenting cells – including dendritic cells, macrophages, and B cells – serve an indispensable role in the adaptive immune response through their unique ability to phagocytose, digest, and present exogenous (circulating) antigens to T cells, facilitating antigen-specific immune responses.
