Memory B cell

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. B cells may also be activated by binding foreign antigen in the periphery where they then move into the secondary lymphoid organs. The TFHs 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. 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. 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. The memory B cells can maintain their BCR expression and will be able to respond quickly upon secondary exposure. == Secondary response and memory ==

The memory B cells produced during the primary immune response are specific to the antigen involved during the first exposure. In a secondary response, the memory B cells specific to the antigen or similar antigens will respond. Moreover, it has been shown that the memory cells that express CD80, PD-L2 and CD73 are more likely to become plasma cells. On the other hand, the cells which don´t have these types of markers are more likely to form germinal center cells. The IgM+ memory B cells do not express CD80 or CD73, whereas IgG+ express them. Moreover, IgG+ are more likely to differentiate into antibody-secreting cells. == Lifespan ==

Memory B cells can survive for decades, which gives them the capacity to respond to multiple exposures to the same antigen. In other experiments in mouse, it has been shown that the lifespan of memory B cells is at least 9 times greater than the lifespan of a follicular naïve B cell. == Markers ==

Memory B cells are typically distinguished by the cell surface marker CD27, although some subsets do not express CD27. Memory B cells that lack CD27 are generally associated with exhausted B cells or certain autoimmune conditions such as HIV, lupus, or rheumatoid arthritis. The receptor CCR6 is generally a marker of B cells that will eventually differentiate into MBCs. This receptor detects chemokines, which are chemical messengers that allow the B cell to move within the body. Memory B cells may have this receptor to allow them to move out of the germinal center and into the tissues where they have a higher probability of encountering antigen. == Subsets ==

Germinal center independent memory B cells This subset of cells differentiates from activated B cells into memory B cells before entering the germinal center. B cells that have a high level of interaction with TFH within the B cell follicle have a higher propensity of entering the germinal center. The B cells that develop into memory B cells independently from germinal centers likely experience CD40 and cytokine signaling from T cells. T-bet memory B cells T-bet B cells are a subset that have been found to express the transcription factor T-bet. T-bet is associated with class switching. T-bet B cells are also thought to be important in immune responses against intracellular bacterial and viral infections. == 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. Long-lived plasma cells and memory B cells are responsible for the long-term humoral immunity elicited by most vaccines. An experiment has been carried in order to observe the longevity of memory B cells after vaccination, in this case with the smallpox vaccine (DryVax), which was selected due to the fact that smallpox was eradicated, so the immune memory to smallpox is a useful benchmark to understand the longevity of the immune memory B cells in the absence of restimulation. The study concluded that the specific memory B cells are maintained for decades, indicating that the immunological memory is long-lived in the B cell compartment after a robust initial antigen exposure. == See also ==