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In immunology, a memory B cell (MBC) is a type of B lymphocyte that forms part of the adaptive immune system. They develop within germinal centers of the secondary lymphoid organs. Memory B cells circulate in the blood stream in a quiescent state, sometimes for decades. Their function is to memorize the characteristics of the antigen that activated their parent B cell during initial infection such that a if the memory B cell later encounters the same antigen, it triggers an accelerated and robust secondary immune response. Memory B cells have B cell receptors (BCRs) on their cell membrane, identical to the one on their parent cell, that allow them to recognize antigen and mount a specific antibody response.

T cell dependent mechanisms
In a T-cell dependent development pathway, naïve follicular B cells are activated by antigen presenting follicular B helper T cells (TFH) during the initial infection, or primary immune response. Naïve B cells circulate through follicles in secondary lymphoid organs (i.e. spleen and lymph nodes) where they can be activated by a floating foreign peptide brought in through the lymph or by antigen presented by antigen presenting cells (APCs) such as dendritic cells (DCs). B cells may also be activated by binding foreign antigen in the periphery where they then move into the secondary lymphoid organs. A signal transduced by the binding of the peptide to the B cell causes the cells to migrate to the edge of the follicle bordering the T cell area.

The B cells internalize the foreign peptides, break them down, and express them on class II major histocompatibility complexe s (MHCII), which are cell surface proteins. Within the secondary lymphoid organs, most of the B cells will enter B-cell follicles where a germinal center will form. Most B cells will eventually differentiate into plasma cells or memory B cells within the germinal center. The TFH s that express T cell receptors (TCRs) cognate to the peptide (i.e. specific for the peptide-MHCII complex) at the border of the B cell follicle and T-cell zone will bind to the MHCII ligand. The T cells will then express the CD40 ligand (CD40L) molecule and will begin to secrete cytokines which cause the B cells to proliferate and to undergo class switch recombination, a mutation in the B cell's genetic coding that changes their immunoglobulin type. Class switching allows memory B cells to secrete different types of antibodies in future immune responses. The B cells then either differentiate into plasma cells, germinal center B cells, or memory B cells depending on the expressed transcription factors. The activated B cells that expressed the transcription factor Bcl-6 will enter B-cell follicles and undergo germinal center reactions.

Once inside the germinal center, the B cells undergo proliferation, followed by mutation of the genetic coding region of their BCR, a process known as somatic hypermutation. The mutations will either increase or decrease the affinity of the surface receptor for a particular antigen, a progression called affinity maturation. After acquiring these mutations, the receptors on the surface of the B cells (B cell receptors) are tested within the germinal center for their affinity to the current antigen. B cell clones with mutations that have increased the affinity of their surface receptors receive survival signals via interactions with their cognate TFH cells. The B cells that do not have high enough affinity to receive these survival signals, as well as B cells that are potentially auto-reactive, will be selected against and die through apoptosis. These processes increase variability at the antigen binding sites such that every newly generated B cell has a unique receptor.

After differentiation, memory B cells relocate to the periphery of the body where they will be more likely to encounter antigen in the event of a future exposure. Many of the circulating B cells become concentrated in areas of the body that have a high likelihood of coming into contact with antigen, such as the Peyer's patch.

The process of differentiation into memory B cells within the germinal center is not yet fully understood. Some researchers hypothesize that differentiation into memory B cells occurs randomly. Other hypotheses propose that the transcription factor NF-κB and the cytokine IL-24 are involved in the process of differentiation into memory B cells. An additional hypothesis states that the B cells with relatively lower affinity for antigen will become memory B cells, in contrast to B cells with relatively higher affinity that will become plasma cells.

T cell independent mechanisms
Not all B cells present in the body have undergone somatic hypermutations. IgM+ memory B cells that have not undergone class switch recombination demonstrate that memory B cells can be produced independently of the germinal centers.

Primary response
Upon infection with a pathogen, many B cells will differentiate into the plasma cells, also called effector B cells, which produce a first wave of protective antibodies and help clear infection. Plasma cells secrete antibodies specific for the pathogens but they cannot respond upon secondary exposure. A fraction of the B cells with BCRs cognate to the antigen differentiate into memory B cells that survive long-term in the body. The memory B cells can maintain their BCR expression and will be able to respond quickly upon secondary exposure.

Vaccination
Vaccines are based on the notion of immunological memory. The preventative injection of a non-pathogenic antigen into the organism allows the body to generate a durable immunological memory. The injection of the antigen leads to an antibody response followed by the production of memory B cells. These memory B cells are promptly reactivated upon infection with the antigen and can effectively protect the organism from disease.