Plasma cell

Plasma cells, also called plasma B cells, plasmocytes, plasmacytes, or effector B cells, are white blood cells that originate in the bone marrow and secrete large quantities of proteins called antibodies in response to being presented specific substances called antigens. These antibodies are transported from the plasma cells by the blood plasma and the lymphatic system to the site of the target antigen (foreign substance), where they initiate its neutralization or destruction. B cells differentiate into plasma cells that produce antibody molecules closely modelled after the receptors of the precursor B cell. . Plasma cells, also called plasma B cells, plasmocytes, plasmacytes, or effector B cells, are white blood cells that originate in the bone marrow and secrete large quantities of proteins called antibodies in response to being presented specific substances called antigens. These antibodies are transported from the plasma cells by the blood plasma and the lymphatic system to the site of the target antigen (foreign substance), where they initiate its neutralization or destruction. B cells differentiate into plasma cells that produce antibody molecules closely modelled after the receptors of the precursor B cell. . Plasma cells are large lymphocytes with a considerable nucleus-to-cytoplasm ratio and a characteristic appearance on light microscopy. They have amphophilic 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. Other organelles in a plasma cell include ribosomes, lysosomes, mitochondria, and the plasma membrane. Terminally differentiated plasma cells express relatively few surface antigens, and do not express common pan-B cell markers, such as CD19 and CD20. Instead, plasma cells are identified through flow cytometry by their additional expression of CD138, 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++. The surface antigen CD138 (syndecan-1) is expressed at high levels. Another important surface antigen is CD319 (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. 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 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. This is a type of safeguard to the system, almost like a two-factor authentication method. First, the B cells have to encounter a foreign antigen, and are then required to be activated by T helper cells before they differentiate to specific cells. 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. 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. 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. 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/PRDM1 and IRF4. After the process of affinity maturation in germinal centers, plasma cells have an indeterminate lifespan, ranging from days to months. Recently they have been shown to reside for much longer periods in the bone marrow as long-lived plasma cells (LLPC). 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.