Genes are fundamental units of heredity, carrying instructions that direct the development and functioning of all living organisms. These instructions are encoded within DNA, dictating the production of specific proteins that perform diverse roles within the body. The CD21 gene plays a role in the immune system. Understanding its function provides insight into how the body defends against pathogens and maintains overall well-being.
Understanding the CD21 Gene
The CD21 gene is formally known as Complement Receptor 2 (CR2). It is located on human chromosome 1 at band 1q32.2. The CD21 gene encodes the CD21 protein, a transmembrane protein with a molecular weight of 140 kDa.
This protein is expressed on the surface of various immune cells, particularly B lymphocytes and follicular dendritic cells. Structurally, the CD21 protein is part of the receptors of complement activation (RCA) family. It is composed of multiple “sushi” or “short consensus repeat” (SCR) domains, each roughly 60-70 amino acids long, which facilitate its interactions with other molecules.
CD21’s Role in Immune Function
The CD21 protein plays a role in immune function, primarily acting as a receptor for certain complement proteins. The complement system is a network of proteins that forms part of the innate immune system, recognizing and clearing pathogens. CD21 binds to activated fragments of complement component C3, such as C3d, iC3b, and C3dg.
On B cells, CD21 forms a complex with other proteins, including CD19 and CD81, known as the B cell co-receptor complex. When a B cell encounters an antigen bound by complement fragments, CD21’s binding helps to lower the threshold for B cell activation, enhancing the B cell’s response and promoting antibody production. This co-receptor function links the innate immune system’s early detection of pathogens with the adaptive immune system’s ability to mount a specific and long-lasting response.
CD21 is also present on follicular dendritic cells (FDCs) within lymph nodes. On FDCs, CD21, along with CD35, acts as a primary receptor for the uptake and retention of immune complexes, which are collections of antigens bound to antibodies and complement proteins. This retention of antigens by FDCs is important for presenting them to B cells, contributing to immune responses and the development of memory B cells.
CD21 and Associated Health Conditions
Dysfunction or deficiency of the CD21 protein can have implications for immune health. One association is with certain immunodeficiencies, such as Common Variable Immunodeficiency (CVID). Patients with CVID may exhibit an expansion of B cells with low CD21 expression, linked to impaired immune function and reduced antibody production. These CD21-low B cells may also be associated with autoimmune conditions due to their pre-activated state and potential for altered immunoglobulin M (IgM) release.
The CD21 protein also serves as the primary receptor for the Epstein-Barr Virus (EBV), a common human herpesvirus. EBV utilizes CD21 to infect B lymphocytes and epithelial cells in the oropharynx, leading to a lifelong infection. In adolescents, primary EBV infection can result in infectious mononucleosis, characterized by symptoms like fatigue, fever, and swollen lymph nodes.
EBV infection, particularly in individuals with compromised immune systems, is linked to B cell lymphomas and other cancers. The virus’s ability to manipulate B cell development and prevent programmed cell death through CD21 binding can contribute to uncontrolled B cell proliferation and lead to lymphoma. Disruptions in CD21’s normal function can therefore contribute to both immunodeficiency and the development of certain virus-related cancers.