Plasma cells, also called plasma B cells or effector B cells, are
white blood cells
White blood cells, also called leukocytes or leucocytes, are the cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. All white blood cells are produced and derived from mult ...
that originate in the
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 ...
as
B lymphocytes
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 ...
and secrete large quantities of proteins called
antibodies in response to being presented specific substances called
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 respons ...
s. These antibodies are transported from the plasma cells by the
blood plasma
Blood plasma is a light amber-colored liquid component of blood in which blood cells are absent, but contains proteins and other constituents of whole blood in suspension. It makes up about 55% of the body's total blood volume. It is the intr ...
and the
lymphatic system to the site of the target
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 respons ...
(foreign substance), where they initiate its neutralization or destruction.
B cells differentiate into plasma cells that produce antibody molecules closely modeled after the receptors of the precursor B cell.
Structure
![Dutcher and Russell bodies](https://upload.wikimedia.org/wikipedia/commons/c/ca/Dutcher_and_Russell_bodies.jpg)
Plasma cells are large
lymphocyte
A lymphocyte is a type of white blood cell (leukocyte) in the immune system of most vertebrates. Lymphocytes include natural killer cells (which function in cell-mediated, cytotoxic innate immunity), T cells (for cell-mediated, cytotoxic ad ...
s with abundant
cytoplasm
In cell biology, the cytoplasm is all of the material within a eukaryotic cell, enclosed by the cell membrane, except for the cell nucleus. The material inside the nucleus and contained within the nuclear membrane is termed the nucleoplasm. ...
and a characteristic appearance on
light microscopy. They have
basophilic
Basophilic is a technical term used by pathologists. It describes the appearance of cells, tissues and cellular structures as seen through the microscope after a histological section has been stained with a basic dye. The most common such dye i ...
cytoplasm and an eccentric nucleus with
heterochromatin in a characteristic cartwheel or clock face arrangement. Their cytoplasm also contains a pale zone that on
electron microscopy contains an extensive
Golgi apparatus
The Golgi apparatus (), also known as the Golgi complex, Golgi body, or simply the Golgi, is an organelle found in most eukaryotic cells. Part of the endomembrane system in the cytoplasm, it packages proteins into membrane-bound vesicles ...
and
centrioles
EM picture. Abundant
rough endoplasmic reticulum
The endoplasmic reticulum (ER) is, in essence, the transportation system of the eukaryotic cell, and has many other important functions such as protein folding. It is a type of organelle made up of two subunits – rough endoplasmic reticulum ( ...
combined with a well-developed Golgi apparatus makes plasma cells well-suited for secreting immunoglobulins. Other
organelles in a plasma cell include ribosomes, lysosomes, mitochondria, and the plasma membrane.
Surface antigens
Terminally differentiated plasma cells express relatively few surface antigens, and do not express common pan-B cell markers, such as
CD19 and
CD20
B-lymphocyte antigen CD20 or CD20 is expressed on the surface of all B-cells beginning at the pro-B phase ( CD45R+, CD117+) and progressively increasing in concentration until maturity.
In humans CD20 is encoded by the ''MS4A1'' gene.
This gene ...
. Instead, plasma cells are identified through
flow cytometry by their additional expression of
CD138
Syndecan 1 is a protein which in humans is encoded by the ''SDC1'' gene. The protein is a transmembrane (type I) heparan sulfate proteoglycan and is a member of the syndecan proteoglycan family. The syndecan-1 protein functions as an integral m ...
,
CD78 CD78 is a protein expressed on the surface of some immature and all mature B-cells. It is considered a pan-B cell antigen. Other names include ''Cdw78, Ba antigen, Leu21'' and ''LO-panB-a''.
Function
It is part of the MHC class II.
Expression
CD ...
, and the
Interleukin-6 receptor
Interleukin 6 receptor (IL6R) also known as CD126 (Cluster of Differentiation 126) is a type I cytokine receptor.
Function
Interleukin 6 (IL6) is a potent pleiotropic cytokine that regulates cell growth and differentiation and plays an importa ...
. In humans,
CD27
CD27 is a member of the tumor necrosis factor receptor superfamily. It is currently of interest to immunologists as a co-stimulatory immune checkpoint molecule, and is the target of an anti-cancer drug in clinical trials.
Expression
During mous ...
is a good marker for plasma cells; naïve B cells are CD27−, memory B-cells are CD27+ and plasma cells are CD27++.
The surface antigen
CD138
Syndecan 1 is a protein which in humans is encoded by the ''SDC1'' gene. The protein is a transmembrane (type I) heparan sulfate proteoglycan and is a member of the syndecan proteoglycan family. The syndecan-1 protein functions as an integral m ...
(syndecan-1) is expressed at high levels.
Another important surface antigen is
CD319
SLAM family member 7 is a protein that in humans is encoded by the ''SLAMF7'' gene.
The surface antigen CD319 (SLAMF7) is a robust marker of normal plasma cells and malignant plasma cells in multiple myeloma. In contrast to CD138 (the traditiona ...
(SLAMF7). This antigen is expressed at high levels on normal human plasma cells. It is also expressed on malignant plasma cells in multiple myeloma. Compared with CD138, which disappears rapidly ex vivo, the expression of CD319 is considerably more stable.
Development
After leaving the bone marrow, the B cell acts as an
antigen-presenting cell (APC) and internalizes offending antigens, which are taken up by the B cell through
receptor-mediated endocytosis and processed. Pieces of the antigen (which are now known as ''antigenic peptides'') are loaded onto
MHC II
MHC Class II molecules are a class of major histocompatibility complex (MHC) molecules normally found only on professional antigen-presenting cells such as dendritic cells, mononuclear phagocytes, some endothelial cells, thymic epithelial cells, ...
molecules, and presented on its extracellular surface to
CD4+ T cells
The T helper cells (Th cells), also known as CD4+ cells or CD4-positive cells, are a type of T cell that play an important role in the adaptive immune system. They aid the activity of other immune cells by releasing cytokines. They are consider ...
(sometimes called ''T helper cells''). These T cells bind to the MHC II-antigen molecule and cause activation of the B cell. This is a type of safeguard to the system, similar to a
two-factor authentication
Multi-factor authentication (MFA; encompassing two-factor authentication, or 2FA, along with similar terms) is an electronic authentication method in which a user is granted access to a website or application only after successfully presenting ...
method. First, the B cells must encounter a foreign antigen and are then required to be activated by T helper cells before they differentiate into specific cells.
Upon stimulation by a T cell, which usually occurs in
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 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 ...
such as the
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 nodes
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 ...
, the activated B cell begins to differentiate into more specialized cells.
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 ...
B cells may differentiate into
memory B cells
In immunology, a memory B cell (MBC) is a type of B lymphocyte that forms part of the adaptive immune system. These cells develop within germinal centers of the secondary lymphoid organs. Memory B cells circulate in the blood stream in a quiesce ...
or plasma cells. Most of these B cells will become plasmablasts (or "immature plasma cells"), and eventually plasma cells, and begin producing large volumes of antibodies. Some B cells will undergo a process known as
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 ...
.
This process favors, by selection for the ability to bind antigen with higher affinity, the activation and growth of B cell clones able to secrete antibodies of higher affinity for the antigen.
Immature plasma cells
![Plasmablast, Wright stain](https://upload.wikimedia.org/wikipedia/commons/0/0e/Plasmablast%2C_Wright_stain.png)
The most immature blood cell that is considered of plasma cell lineage is the plasmablast.
Plasmablasts secrete more antibodies than B cells, but less than plasma cells.
They divide rapidly and are still capable of internalizing antigens and presenting them to T cells.
A cell may stay in this state for several days, and then either die or irrevocably differentiate into a mature, fully differentiated plasma cell.
Differentiation of mature B cells into plasma cells is dependent upon the transcription factors
Blimp-1
PR domain zinc finger protein 1, or B lymphocyte-induced maturation protein-1 (BLIMP-1), is a protein in humans encoded by the gene ''PRDM1'' located on chromosome 6q21. BLIMP-1 is considered a 'master regulator' of hematopoietic stem cells, and p ...
/
PRDM1
PR domain zinc finger protein 1, or B lymphocyte-induced maturation protein-1 (BLIMP-1), is a protein in humans encoded by the gene ''PRDM1'' located on chromosome 6q21. BLIMP-1 is considered a 'master regulator' of hematopoietic stem cells, and p ...
and
IRF4
Interferon regulatory factor 4 (IRF4) also known as ''MUM1'' is a protein that in humans is encoded by the ''IRF4'' gene, located at 6p25-p23. IRF4 functions as a key regulatory transcription factor in the development of human immune cells.Nam S, ...
.
Function
Unlike their precursors, plasma cells cannot
switch antibody classes, cannot act as antigen-presenting cells because they no longer display MHC-II, and do not take up antigen because they no longer display significant quantities of immunoglobulin on the cell surface.
However, continued exposure to antigen through those low levels of immunoglobulin is important, as it partly determines the cell's lifespan.
The lifespan, class of antibodies produced, and the location that the plasma cell moves to also depends on signals, such as
cytokines, received from the T cell during differentiation.
Differentiation through a T cell-independent antigen stimulation (stimulation of a B cell that does not require the involvement of a T cell) can happen anywhere in the body
and results in short-lived cells that secrete IgM antibodies.
The T cell-dependent processes are subdivided into primary and secondary responses: a primary response (meaning that the T cell is present at the time of initial contact by the B cell with the antigen) produces short-lived cells that remain in the extramedullary regions of lymph nodes; a secondary response produces longer-lived cells that produce IgG and IgA, and frequently travel to the bone marrow.
For example, plasma cells will likely secrete
IgG3 antibodies if they matured in the presence of the cytokine
interferon-gamma
Interferon gamma (IFN-γ) is a dimerized soluble cytokine that is the only member of the type II class of interferons. The existence of this interferon, which early in its history was known as immune interferon, was described by E. F. Wheeloc ...
. Since B cell maturation also involves
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 ...
(a process completed before differentiation into a plasma cell), these antibodies frequently have a very high affinity for their antigen.
Plasma cells can only produce a single kind of antibody in a single class of immunoglobulin. In other words, every B cell is specific to a single antigen, but each cell can produce several thousand matching antibodies per second.
This prolific production of antibodies is an integral part of the
humoral immune response.
Long-lived plasma cells
The current findings suggest that after the process of affinity maturation in germinal centers, plasma cells develop into one of two types of cells: short-lived plasma cells (SLPC) or long-lived plasma cells (LLPC). LLPC mainly reside in the bone marrow for a long period of time and secrete antibodies, thus providing long-term protection. LLPC can maintain antibody production for decades or even for the lifetime of an individual, and, unlike B cells, LLPC do not need antigen restimulation to generate antibodies. Human LLPC population can be identified as
CD19– CD38hi CD138+ cells.
The long-term survival of LLPC are dependent on a specific environment in the bone marrow, the plasma cell survival niche. Removal of an LLPC from its survival niche results in its rapid death. A survival niche can only support limited number of LLPC, thus the niche’s environment must protect its LLPC cells but be able to accept new arrivals. The plasma cell survival niche is defined by a combination of cellular and molecular factors and though it has yet to be properly defined, molecules such as
IL-5,
IL-6,
TNF-α
Tumor necrosis factor (TNF, cachexin, or cachectin; formerly known as tumor necrosis factor alpha or TNF-α) is an adipokine and a cytokine. TNF is a member of the TNF superfamily, which consists of various transmembrane proteins with a homolog ...
,
stromal cell-derived factor-1α and signalling via
CD44
The CD44 antigen is a cell-surface glycoprotein involved in cell–cell interactions, cell adhesion and migration. In humans, the CD44 antigen is encoded by the ''CD44'' gene on chromosome 11. CD44 has been referred to as HCAM (homing cell adhes ...
have been shown to play a role in the survival of LLPC. LLPC can also be found, to a lesser degree, in
gut-associated lymphoid tissue
Gut-associated lymphoid tissue (GALT) is a component of the mucosa-associated lymphoid tissue (MALT) which works in the immune system to protect the body from invasion in the gut.
Owing to its physiological function in food absorption, the mucosa ...
(GALT), where they produce
IgA antibodies and contribute to mucosal immunity. Recent findings suggest that plasma cells in the gut do not necessarily need to be generated ''de novo'' from active B cells but there are also long-lived PC, suggesting the existence of a similar survival niche. Tissue specific niches that allow for the survival of LLPC have been also described in nasal-associated lymphoid tissues (NALT), human tonsillar lymphoid tissues and human mucosa or mucosa-associated lymphoid tissues (MALT).
Originally it was thought that the continuous production of antibodies is a result of constant replenishment of short-lived plasma cells by memory B cell re-stimulation. Recent findings, however, show that some PC are truly long-lived. The absence of antigens and the depletion of B cells does not appear to have an effect on the production of high-affinity antibodies by the LLPC. Prolonged depletion of B cells (with anti-CD20 monoclonal antibody treatment that affects B cells but not PC) also did not affect antibody titres. LLPC secrete high levels of
IgG
Immunoglobulin G (Ig G) is a type of antibody. Representing approximately 75% of serum antibodies in humans, IgG is the most common type of antibody found in blood circulation. IgG molecules are created and released by plasma B cells. Each IgG ...
independently of B cells. LLPC in bone marrow are the main source of circulating IgG in humans. Even though IgA production is traditionally associated with mucosal sites, some plasma cells in bone marrow also produce IgA. LLPC in bone marrow have been observed producing
IgM
Immunoglobulin M (IgM) is one of several isotypes of antibody (also known as immunoglobulin) that are produced by vertebrates. IgM is the largest antibody, and it is the first antibody to appear in the response to initial exposure to an antig ...
.
Clinical significance
Plasmacytoma
Plasmacytoma is a plasma cell dyscrasia in which a plasma cell tumour grows within soft tissue or within the axial skeleton.
The International Myeloma Working Group lists three types: Plasma cell dyscrasia#Solitary plasmacytoma, solitary plasma ...
,
multiple myeloma,
Waldenström macroglobulinemia
Waldenström macroglobulinemia () is a type of cancer affecting two types of B cells: lymphoplasmacytoid cells and plasma cells. Both cell types are white blood cells. It is characterized by having high levels of a circulating antibody, immunogl ...
,
heavy chain disease, and
plasma cell leukemia are
malignant neoplasms
Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal bl ...
("cancer") of the plasma cells.
Multiple myeloma is frequently identified because malignant plasma cells continue producing an antibody, which can be detected as a
paraprotein
A myeloma protein is an abnormal antibody (immunoglobulin) or (more often) a fragment thereof, such as an immunoglobulin light chain, that is produced in excess by an abnormal monoclonal proliferation of plasma cells, typically in multiple myelo ...
.
Common variable immunodeficiency is thought to be due to a problem in the
differentiation from lymphocytes to plasma cells. The result is a low serum antibody level and risk of infections.
Primary amyloidosis (AL) is caused by the deposition of excess immunoglobulin light chains which are secreted from plasma cells.
See also
*
Leukocyte
*
Plasma cell dyscrasia
Plasma cell dyscrasias (also termed plasma cell disorders and plasma cell proliferative diseases) are a spectrum of progressively more severe monoclonal gammopathies in which a clone or multiple clones of pre-malignant or malignant plasma cells ( ...
References
External links
*
Histology at wadsworth.org
{{DEFAULTSORT:Plasma Cell
B cells
Connective tissue cells
Human cells
Immune system
Immunology
Lymphocytes