Plasma cells

Plasma cells, also called plasma B cells, plasmocytes, and effector B cells, are white blood cells that produce large volumes of antibodies. They are transported by the blood plasma and the lymphatic system. Like all blood cells, plasma cells ultimately originate in the bone marrow; however, these cells leave the bone marrow as B cells, before terminal differentiation into plasma cells, which usually happens in lymph nodes.

Development
After leaving the bone marrow, the B cell acts as an antigen presenting cell (APC) and internalizes offending antigens. That antigen is taken up by the B cell through receptor-mediated endocytosis and processed. Pieces of the pathogen (which are now known as antigenic peptides) are loaded onto MHC II molecules, and presented on its extracellular surface to CD4+ T cells (sometimes called T helper cells). These T cells bind to the MHC II/antigen molecule and cause activation of the B cell.

Upon stimulation by a T cell, which usually occurs in germinal centers of secondary lymphoid organs like the spleen and lymph nodes, the activated B cell begins to differentiate into more specialized cells. Germinal center B cells may differentiate into memory B cells or plasma cells. The mechanism by which a B cell becomes one or the other of these three is poorly understood. Most of these B cells will become plasmablasts, and eventually plasma cells, and begin producing large volumes of antibodies.

The most immature blood cell that is considered a plasma cell instead of a B cell 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.

Activity
After the process of affinity maturation in germinal centers, plasma cells have an indeterminate lifespan, ranging from days to months. They secrete high levels of antibodies, ranging from hundreds to thousands of antibodies per second per cell. Unlike their precursors, they 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 depend 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. Since B cell maturation also involves somatic hypermutation (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, 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.

Microscopic anatomy
Plasma cells are large lymphocytes with a considerable nucleus-to-cytoplasm ratio and a characteristic appearance on light microscopy. They have basophilic 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 and centrioles (EM picture). Abundant rough endoplasmic reticulum combined with a well-developed Golgi apparatus makes plasma cells well-suited for secreting immunoglobulins.

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. In humans, CD20 expression is first lost, therefore blood plasma cells (wandering from germinal centers to bone marrow or site of infection) are still CD19+. In mice, CD19 is earlier lost, therefore analysis of blood plasma cells is not possible with a CD19 specific staining, instead you have to use a staining for B220, which is still expressed. Instead, plasma cells are identified through flow cytometry by their additional expression of CD38, CD45, CD78, and the Interleukin-6 receptor. In humans, CD27 is a good marker for plasma cells, naive B cells are CD27-, memory B-cells are CD27+ and plasma cells are CD27++.

CD38 and CD138 are expressed at high levels.

Role in disease
Plasmacytoma, multiple myeloma, Waldenström macroglobulinemia and plasma cell leukemia are malignant neoplasms ("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.

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.