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The hidden secret of longevity: How do plasma cells survive in the bone marrow for decades?
Plasma cells, also known as plasma B cells or effector B cells, are a type of white blood cell that originates from lymphoid organs. When they are faced with specific substances (called antigens), they secrete large amounts of antibodies. These antibodies are transported through the plasma and lymphatic system to the site of the target antigen, initiating the process of neutralizing or destroying the foreign substance. The main task of plasma cells is to protect the body from pathogens.
Plasma cells are large lymphocytes with abundant cytoplasm and a distinctive appearance under the light microscope.
Structurally, plasma cells possess a robust internal structure, including a rough endoplasmic reticulum and highly developed basal bodies, which makes them ideally suited for secreting immunoglobulins. The nuclei of these cells are lateralized and the cytoplasm is basophilic.
In terms of surface antigens, fully differentiated plasma cells display relatively few surface antigens and do not express common pan-B cell markers such as CD19 and CD20. Instead, plasma cells are identified by CD138, CD78, and interleukin-6 receptor.
The life cycle of plasma cells and their ability to produce antibodies depend on a specific microenvironment, particularly their survival zone in the bone marrow.
During the development process, B cells undergo the antigen presentation process, internalize invading antigens, and present them to CD4+ T cells through MHC II molecules for activation. This reflects the role of a protection system, similar to the two-factor authentication method. Cells need to first come into contact with foreign antigens and then be activated by T cells before they can differentiate into specific cells.
Once activated, activated B cells differentiate into more specialized cells in germinal centers in secondary lymphoid organs such as the spleen and lymph nodes. Most of these B cells become plasmablasts, or plasma cells, and begin producing large amounts of antibodies.
The affinity maturation process that occurs in the germinal center enables plasma cells to secrete antibodies with high affinity, which is essential for effectively fighting infection.
Among the two types of plasma cells—short-lived plasma cells and long-lived plasma cells, LLPCs (long-lived plasma cells) mainly survive in the bone marrow and have the ability to produce antibodies for a long time. They provide long-term protection throughout life and do not require antigen restimulation for antibody production. The key to this survival ability lies in the microenvironment in the bone marrow, the area where plasma cells survive.
These long-lived plasma cells serve as the main source of IgG secretion in the bone marrow. Although IgA production has traditionally been associated with mucosal sites, it has been observed that some plasma cells in the bone marrow can also produce IgA.
Plasma cells remaining in the plasma cell survival zone can still efficiently produce antibodies in the absence of antigens and B cells, demonstrating their unique survival and adaptability.
Clinically, cancers involving plasma cells, such as plasmacytoma and myeloma, are characterized by the continuous production of detectable antibodies by malignant plasma cells. In contrast, common variable immunodeficiency is thought to result from a problem with the conversion of B cells to plasma cells, which results in low serum antibody levels and an increased risk of infection.
As we gain a better understanding of plasma cell biology, we can further explore their role in the immune system and how to use this knowledge to address a variety of diseases. In the future, how will scientists use the research results of these long-lived plasma cells to develop new treatments?
