Memory B cell

Memory B cells are a B cell sub-type that are formed within germinal centers following primary infection and are important in generating an accelerated and more robust antibody-mediated immune response in the case of re-infection (also known as a secondary immune response). Memory B cells are a B cell sub-type that are formed within germinal centers following primary infection and are important in generating an accelerated and more robust antibody-mediated immune response in the case of re-infection (also known as a secondary immune response). During an initial infection (or primary immune response) involving a T-dependent antigen, naive follicular B cells are activated in the presence of TFH cells within the follicles of secondary lymphoid organs (i.e. spleen and lymph nodes) and undergo clonal expansion to produce a foci of B cells that are specific for the antigen. Most of these clones differentiate into the plasma cells, also called effector B cells which produce a first wave of protective antibodies and help clear the infection, but a fraction persist as dormant memory cells that survive in the body on a long-term basis after having gone through a highly mutative and selective germinal center reaction. Activated B cells that fail to undergo germinal center differentiation do not persist as effective memory B cells and are rapidly negatively selected against. Within germinal centers, B cells proliferate and mutate the genetic region coding for their surface antibody (also known as immunoglobulin). The process is called somatic hypermutation and is responsible for introducing spontaneous mutations with a frequency of about 1 in every 1600 cell division (a relatively high frequency considering the low mutation frequency of other cells of the body being 1 in 106 cell divisions). Then after gaining a set number of mutations, germinal center B cells are subjected to a round of selection by TFH cells. B cell clones that have mutated and gained higher affinity surface immunoglobulin that better recognize antigen receive cellular contact-dependent survival signals from interacting with their cognate TFH cells and go on to one of three fates: (i) differentiate into plasma cells that have improved affinity towards antigen (therefore more efficient than their earlier the generation of plasma cells in clearing the infection), (ii) affinity matured memory B cells, or (iii) retained in the germinal center to re-enter another round of mutative replication and TFH cell-dependent selection. Therefore, as an infection proceeds, memory B cells selected in the later stages of a germinal center response are found to have accumulated the highest numbers of immunoglobulin mutation events with superior affinity towards their targeted antigen. Conversely, during the course of a germinal center reaction, low affinity or potentially auto-reactive germinal center B cell clones, or those that have gained non-functional mutations are out-competed by higher affinity clones and eventually undergo cellular apoptosis. With each such subsequent exposure to the same antigen, the number of different responding B cell clones increases to generate a polyclonal response and effectively a greater number of memory B cells persist. Thus, a stronger antibody response (i.e. higher titres of more diverse antibody molecules) having improved affinity towards antigen is typically observed in the secondary immune response. It is unclear at what stage such a model reaches saturation to provide an optimal level of antibody-mediated immune protection against the same antigen. However, the fact that all the accumulation of cells of a single clone population express many of the one same type of antibody and that these memory B cells survive for long periods of time in a body underscores their functional significance during vaccination and the administration of booster shots. A typical ability is long-lasting survival in quiescence; this can last for tens of years in humans. After re-encountering the specific antigen they are able to reactivate very quickly, propagate themselves, create plasma cells and reenter germinal centres to improve affinity of their antibodies. Thanks to this, every secondary immune response is stronger than the primary one. The ability to proliferate and create whole B cell population specific to the antigen is sometimes called as a stemness of memory B cells. It seems, that IgM+ memory B cells are the best in this (they have not class-switched their BCR). Long-lasting survival is dependent on metabolic changes and blocking of apoptosis. The presence of follicular dendritic cells (FDC) and tonic signalisation through BCR (basic stimuli from BCR independent on specific antigen) are necessary. These induce expression of anti-apoptotic genes in B cell. The specific antigen does not have to be present to keep memory B cells, neither T cells are necessary. Strong and quick response could be a result of switched BCR. Some isotypes do have a cytoplasmic part which can signal into B cell - mainly it was studied on IgG1. The cytoplasmic domain of IgG1 can interact with components of MAPK cascade and so potentiate the signalling when antigen is recognised. Apart from that, the stimulation history of memory B cell is critical - thanks to that the B cell has changed levels of transcription factors and it`s threshold for stimulation is higher - easier to overcome. Reactivation of memory B cell is dependent on interaction with their cognate memory TFH. Both cell types are present in secondary lymphatic tissues in B follicle and so they can quickly interact, when specific antigen is present. The interaction works probably both sides - first the B cell works as an antigen-presenting cell and activate the TFH, second activated TFH activates the memory B cell. Important role have also FDC, which quickly grab incoming antigens and store them on their surface for B cells - mainly when the antigen is in immune complex.