Memory B Cell
   HOME

TheInfoList



OR:

In
immunology Immunology is a branch of medicineImmunology for Medical Students, Roderick Nairn, Matthew Helbert, Mosby, 2007 and biology that covers the medical study of immune systems in humans, animals, plants and sapient species. In such we can see there ...
, a memory B cell (MBC) is a type of
B lymphocyte 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 ...
that forms part of the
adaptive immune system The adaptive immune system, also known as the acquired immune system, is a subsystem of the immune system that is composed of specialized, systemic cells and processes that eliminate pathogens or prevent their growth. The acquired immune system ...
. These cells develop within
germinal center 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, prolifera ...
s of the
secondary lymphoid organs The lymphatic system, or lymphoid system, is an organ system in vertebrates that is part of the immune system, and complementary to the circulatory system. It consists of a large network of lymphatic vessels, lymph nodes, lymphatic or lymphoid ...
. 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 In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response. ...
that activated their parent B cell during initial infection such that if the memory B cell later encounters the same
antigen In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response. ...
, 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.


Development and activation


T cell dependent mechanisms

In a
T-cell A T cell is a type of lymphocyte. T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell r ...
dependent development pathway, naïve
follicular B cell Within the immune system, Follicular B cells (FO B cells) are a type of B cell that reside in primary and secondary lymphoid follicles (containing germinal centers) of secondary and tertiary lymphoid organs, including spleen and lymph nodes. Antibo ...
s are activated by antigen presenting
follicular B helper T cells Follicular helper T cells (also known as follicular B helper T cells and abbreviated as TFH), are antigen-experienced CD4+ T cells found in the periphery within B cell follicles of secondary lymphoid organs such as lymph nodes, spleen and Peyer's ...
(TFH) during the initial infection, or primary
immune response An immune response is a reaction which occurs within an organism for the purpose of defending against foreign invaders. These invaders include a wide variety of different microorganisms including viruses, bacteria, parasites, and fungi which could ...
. Naïve B cells circulate through follicles in secondary lymphoid organs (i.e.
spleen The spleen is an organ found in almost all vertebrates. Similar in structure to a large lymph node, it acts primarily as a blood filter. The word spleen comes .
and
lymph node A lymph node, or lymph gland, is a kidney-shaped organ of the lymphatic system and the adaptive immune system. A large number of lymph nodes are linked throughout the body by the lymphatic vessels. They are major sites of lymphocytes that inclu ...
s) where they can be activated by a floating foreign peptide brought in through the
lymph Lymph (from Latin, , meaning "water") is the fluid that flows through the lymphatic system, a system composed of lymph vessels (channels) and intervening lymph nodes whose function, like the venous system, is to return fluid from the tissues to ...
or by antigen presented by
antigen presenting cells An antigen-presenting cell (APC) or accessory cell is a cell that displays 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 ...
(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 complexes (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 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
cytokine Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in autocrin ...
s which cause the B cells to proliferate and to undergo
class switch recombination Immunoglobulin class switching, also known as isotype switching, isotypic commutation or class-switch recombination (CSR), is a biological mechanism that changes a B cell's production of immunoglobulin from one type to another, such as from the ...
, a mutation in the B cell's genetic coding that changes their
immunoglobulin An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...
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 factor In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The fu ...
s. 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 Somatic hypermutation (or SHM) is a cellular mechanism by which the immune system adapts to the new foreign elements that confront it (e.g. microbes), as seen during class switching. A major component of the process of affinity maturation, SHM div ...
. The mutations will either increase or decrease the affinity of the surface receptor for a particular antigen, a progression called
affinity maturation In immunology, affinity maturation is the process by which TFH cell-activated B cells produce antibodies with increased affinity for antigen during the course of an immune response. With repeated exposures to the same antigen, a host will produc ...
. 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 Peyer's patches (or aggregated lymphoid nodules) are organized lymphoid follicles, named after the 17th-century Swiss anatomist Johann Conrad Peyer. * Reprinted as: * Peyer referred to Peyer's patches as ''plexus'' or ''agmina glandularum'' (c ...
. 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 In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The fu ...
NF-κB and the
cytokine Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in autocrin ...
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 An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...
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.


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. When memory B cells reencounter their specific antigen, they proliferate and differentiate into plasma cells, which then respond to and clear the antigen. The memory B cells that do not differentiate into plasma cells at this point can reenter the germinal centers to undergo further class switching or somatic hypermutation for further affinity maturation. Differentiation of memory B cells into plasma cells is far faster than differentiation by naïve B cells, which allows memory B cells to produce a more efficient secondary immune response. The efficiency and accumulation of the memory B cell response is the foundation for vaccines and booster shots. The phenotype of memory cells that prognosticate plasma cells or germinal center cells fate has been discovered  few years ago. Based on expression microarray comparisons between memory B cells and naïve B cells, it was identified that there are several surface proteins, such as
CD80 The Cluster of differentiation 80 (also CD80 and B7-1) 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 cl ...
, PD-L2 and CD73 that are only expressed on the memory B cells, so they also serve to divide this cells in multiple phenotypic subsets. 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 type 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 differenciate 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. The long-lasting survival is hypothesized to be a result of certain anti-apoptosis genes that are more highly expressed in memory B cells than other subsets of B cells. Additionally, the memory B cell does not need to have continual interaction with the antigen nor with T cells in order to survive long-term. However, it is true that the lifespan of individual memory B cells remains poorly defined, although they have a critical role in long-term immunity. In one study using a
B cell receptor The B cell receptor (BCR) is a transmembrane protein on the surface of a B cell. A B cell receptor is composed of a membrane-bound immunoglobulin molecule and a signal transduction moiety. The former forms a type 1 transmembrane receptor protein, ...
(BCR) transgenic system (it was a H chain transgenic mouse model which lacked secreted Ig, so it didn´t deposit Ag-containing immune complexes), it was shown that the number of memory B cells remain constant for a period of around 8–20 weeks after the immunization. It was also estimated that the
half-life Half-life (symbol ) is the time required for a quantity (of substance) to reduce to half of its initial value. The term is commonly used in nuclear physics to describe how quickly unstable atoms undergo radioactive decay or how long stable ato ...
of memory B cells was between 8–10 weeks, after doing an experiment in which the cells were treated in vivo with
bromodeoxyuridine Bromodeoxyuridine (5-bromo-2'-deoxyuridine, BrdU, BUdR, BrdUrd, broxuridine) is a synthetic nucleoside analogue with a chemical structure similar to thymidine. BrdU is commonly used to study cell proliferation in living tissues and has been stud ...
. 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. Because B cells have typically undergone class switching, they can express a range of
immunoglobulin An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...
molecules. Some specific attributes of particular immunoglobulin molecules are described below:   * IgM: Memory B cells that express IgM can be found concentrated in the
tonsils The tonsils are a set of lymphoid organs facing into the aerodigestive tract, which is known as Waldeyer's tonsillar ring and consists of the adenoid tonsil, two tubal tonsils, two palatine tonsils, and the lingual tonsils. These organs play a ...
, Peyer's patch, and lymph nodes. This subset of memory B cells is more likely to proliferate and reenter the germinal center during a secondary immune response. * IgG: Memory B cells that express IgG typically differentiate into plasma cells. * IgE: Memory B cells that express IgE are very rare in healthy individuals. This may occur because B cells that express IgE more frequently differentiate into plasma cells rather than memory B cells * IgD only: Memory B cells that express IgD are very rare. B cells with only IgD are found concentrated in the tonsils. It is important to mention the importance of integration of signalling pathways related to the recepetors of BCRs and TLRs in order to modulate the production of the antibodies by the expansion of the memory B cells. Therefore, there are different factors that provide the information in order to secret different types of antibodies. It has been demonstrated that the production of specific-IgG1, anaphylactic-IgG1 and total-IgE depends on the signal produce by
TLR2 Toll-like receptor 2 also known as TLR2 is a protein that in humans is encoded by the ''TLR2'' gene. TLR2 has also been designated as CD282 (cluster of differentiation 282). TLR2 is one of the toll-like receptors and plays a role in the immune sys ...
and Myd88. Moreover, the signal produce by
TLR4 Toll-like receptor 4 is a protein that in humans is encoded by the ''TLR4'' gene. TLR4 is a transmembrane protein, member of the toll-like receptor family, which belongs to the pattern recognition receptor (PRR) family. Its activation leads to an ...
when it is stimulated by natterins (protein obtained from ''T. nattereri'' fish venom) accelerates the synthesis of the antibody IgE acting as an adjuvant, as it was shown in an in vivo experiment with mice. The receptor CCR6 is generally a marker of B cells that will eventually differentiate into MBCs. This receptor detects
chemokine Chemokines (), or chemotactic cytokines, are a family of small cytokines or signaling proteins secreted by cells that induce directional movement of leukocytes, as well as other cell types, including endothelial and epithelial cells. In additio ...
s, 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. It has been shown that memory B cells have high level expression of CCR6 as well as an increased chemotactic response to the CCR6 ligand (
CCL20 Chemokine (C-C motif) ligand 20 (CCL20) or liver activation regulated chemokine (LARC) or Macrophage Inflammatory Protein-3 (MIP3A) is a small cytokine belonging to the CC chemokine family. It is strongly chemotactic for lymphocytes and weakly at ...
) in comparison with naïve B cells. Nevertheless, the primary humoral response and the maintenance of the memory B cells are not affected in CCR6-deficient mice. However, there is not an effective secondary response  from the memory B cells when there is a reexposure of the antigen if the cells do not express CCR6. Therefore we can confirm that CCR6 is essential for the ability of memory B cells to be recalled to their cognate antigen as well as for the appropriate anatomical positioning of these cells.


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. Class switching can still occur prior to interaction with the germinal center, while somatic hypermutation only occurs after interaction with the germinal center. The lack of somatic hypermutation is hypothesized to be beneficial; a lower level of affinity maturation means that these memory B cells are less specialized to a specific antigen and may be able to recognize a wider range of antigens. T-independent memory B cells T-independent memory B cells are a subset called B1 cells. These cells generally reside in the peritoneal cavity. When reintroduced to antigen, some of these B1 cells can differentiate into memory B cells without interacting with a T cell. These B cells produce IgM antibodies to help clear infection. 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

Vaccine A vaccine is a biological Dosage form, preparation that provides active acquired immunity to a particular infectious disease, infectious or cancer, malignant disease. The safety and effectiveness of vaccines has been widely studied and verifie ...
s are based on the notion of
immunological memory Immunological memory is the ability of the immune system to quickly and specifically recognize an antigen that the body has previously encountered and initiate a corresponding immune response. Generally, these are secondary, tertiary and other subs ...
. The preventative injection of a non-pathogenic
antigen In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response. ...
into the organism allows the body to generate a durable
immunological memory Immunological memory is the ability of the immune system to quickly and specifically recognize an antigen that the body has previously encountered and initiate a corresponding immune response. Generally, these are secondary, tertiary and other subs ...
. 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 The smallpox vaccine is the first vaccine to be developed against a contagious disease. In 1796, British physician Edward Jenner demonstrated that an infection with the relatively mild cowpox virus conferred immunity against the deadly smallpox ...
(DryVax), which was selected due to the fact that
smallpox Smallpox was an infectious disease caused by variola virus (often called smallpox virus) which belongs to the genus Orthopoxvirus. The last naturally occurring case was diagnosed in October 1977, and the World Health Organization (WHO) c ...
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

*
Memory T cell Memory T cells are a subset of T lymphocytes that might have some of the same functions as memory B cells. Their lineage is unclear. Function Antigen-specific memory T cells specific to viruses or other microbial molecules can be found in both ...


References

{{DEFAULTSORT:Memory B Cell B cells Lymphocytes Human cells Immunology Immune system ru:B-лимфоциты