B cell

development: from immature B cell to MZ B cell or mature (FO) B cell B cells develop from hematopoietic stem cells (HSCs) that originate from bone marrow. HSCs first differentiate into multipotent progenitor (MPP) cells, then common lymphoid progenitor (CLP) cells. B cells undergo two types of selection while developing in the bone marrow to ensure proper development, both involving B cell receptors (BCR) on the surface of the cell. Positive selection occurs through antigen-independent signalling involving both the pre-BCR and the BCR. If these receptors do not bind to their ligand, B cells do not receive the proper signals and cease to develop. Throughout their migration to the spleen and after spleen entry, they are considered T1 B cells. Within the spleen, T1 B cells transition to T2 B cells. Once differentiated, they are now considered mature B cells, or naïve B cells. ==Activation==

that secretes large numbers of antibodies B cell activation occurs in the secondary lymphoid organs (SLOs), such as the spleen and lymph nodes. At the SLO, B cell activation begins when the B cell binds to an antigen via its BCR. Although the events taking place immediately after activation have yet to be completely determined, it is believed that B cells are activated in accordance with the kinetic segregation model , initially determined in T lymphocytes. This model denotes that before antigen stimulation, receptors diffuse through the membrane coming into contact with Lck and CD45 in equal frequency, rendering a net equilibrium of phosphorylation and non-phosphorylation. It is only when the cell comes in contact with an antigen presenting cell that the larger CD45 is displaced due to the close distance between the two membranes. This allows for net phosphorylation of the BCR and the initiation of the signal transduction pathway. Of the three B cell subsets, FO B cells preferentially undergo T cell-dependent activation while MZ B cells and B1 B cells preferentially undergo T cell-independent activation. B cell activation is enhanced through the activity of CD21, a surface receptor in complex with surface proteins CD19 and CD81 (all three are collectively known as the B cell coreceptor complex). When a BCR binds an antigen tagged with a fragment of the C3 complement protein, CD21 binds the C3 fragment, co-ligates with the bound BCR, and signals are transduced through CD19 and CD81 to lower the activation threshold of the cell. T cell-dependent activation Antigens that activate B cells with the help of T-cell are known as T cell-dependent (TD) antigens and include foreign proteins. T helper (TH) cells, typically follicular T helper (TFH) cells recognize and bind these MHC-II-peptide complexes through their T cell receptor (TCR). Following TCR-MHC-II-peptide binding, T cells express the surface protein CD40L as well as cytokines such as IL-4 and IL-21. , with germinal center in the middle. The second step consists of activated B cells entering a lymphoid follicle and forming a germinal center (GC), which is a specialized microenvironment where B cells undergo extensive proliferation, immunoglobulin class switching, and affinity maturation directed by somatic hypermutation. These processes are facilitated by TFH and follicular dendritic cells within the GC and generate both high-affinity memory B cells and long-lived plasma cells. Resultant plasma cells secrete large numbers of antibodies and either stay within the SLO or, more preferentially, migrate to bone marrow. Memory B cell activation Memory B cell activation begins with the detection and binding of their target antigen, which is shared by their parent B cell. Some memory B cells can be activated without T cell help, such as certain virus-specific memory B cells, but others need T cell help. == B cell types ==

. ; Plasmablast: A short-lived, proliferating antibody-secreting cell arising from B cell differentiation. ; Memory B cell: Dormant B cell arising from B cell differentiation. Memory B cells can be generated from T cell-dependent activation through both the extrafollicular response and the germinal center reaction as well as from T cell-independent activation of B1 cells. They can undergo both T cell-independent and T cell-dependent activation, but preferentially undergo T cell-independent activation. In mice, they predominantly populate the peritoneal cavity and pleural cavity, generate natural antibodies (antibodies produced without infection), defend against mucosal pathogens, and primarily exhibit T cell-independent activation. Also, it promotes the generation of regulatory T (Treg) cells by directly interacting with T cells to skew their differentiation towards Tregs. No common Breg cell identity has been described and many Breg cell subsets sharing regulatory functions have been found in both mice and humans. It is currently unknown if Breg cell subsets are developmentally linked and how exactly differentiation into a Breg cell occurs. There is evidence showing that nearly all B cell types can differentiate into a Breg cell through mechanisms involving inflammatory signals and BCR recognition. ==B cell-related pathology==

Autoimmune disease can result from abnormal B cell recognition of self-antigens followed by the production of autoantibodies. Autoimmune diseases where disease activity is correlated with B cell activity include scleroderma, multiple sclerosis, systemic lupus erythematosus, type 1 diabetes, post-infectious IBS, and rheumatoid arthritis. Abnormal B cells may be relatively large and some diseases include this in their names, such as diffuse large B-cell lymphomas (DLBCLs) and intravascular large B-cell lymphoma. Patients with B cell alymphocytosis are predisposed to infections. == Epigenetics ==

A study that investigated the methylome of B cells along their differentiation cycle, using whole-genome bisulfite sequencing (WGBS), showed that there is a hypomethylation from the earliest stages to the most differentiated stages. The largest methylation difference is between the stages of germinal center B cells and memory B cells. Furthermore, this study showed that there is a similarity between B cell tumors and long-lived B cells in their DNA methylation signatures. == See also ==