CD93

CD93 (Cluster of Differentiation 93) is a is_associated_with::protein that in humans is encoded by the CD93 is_associated_with::gene. CD93 is a is_associated_with::C-type lectin transmembrane receptor which play a role not only in cell–cell adhesion processes but also in host defence.

Family
CD93 belongs to the Group XIV C-Type is_associated_with::lectin family, a group containing two other members, endosialin (is_associated_with::CD248) and is_associated_with::thrombomodulin, a well characterized anticoagulant. All of them contain a C-type lectin domain, a series of epidermal growth factor like domains (EGF), a highly glycosylated mucin-like domain, a unique transmembrane domain and a short cytoplasmic tail. Due to their strong homology and their close proximity on chromosome 20, CD93 has been suggested to have arisen from the thrombomodulin gene through a duplication event

Expression
CD93 was originally identified in mice as an early is_associated_with::B cell marker through the use of AA4.1 monoclonal antibody. Then this molecule was shown to be expressed on an early population of is_associated_with::hematopoietic stem cells, which give rise to the entire spectrum of mature cells in the blood. Now CD93 is known to be expressed by a wide variety of cells such as is_associated_with::platelets, is_associated_with::monocytes, is_associated_with::microglia and endothelial cells. In the immune system CD93 is also expressed on is_associated_with::neutrophils, activated is_associated_with::macrophages, B cell precursors until the T2 stage in the spleen, a subset of dendritic cells and of natural killer cells. Molecular characterization of CD93 revealed that this protein is identical with C1qRp, a human protein identified as a putative C1q receptor. C1q belongs to the complement activation proteins and plays a major role in the activation of the classical pathway of the complement, which leads to the formation of the membrane attack complex. C1q is also involved in other immunological processes such as enhancement of bacterial phagocytosis, clearance of apoptotic cells or neutralisation of virus. Strikingly, it has been shown that anti-C1qRp significantly reduced C1q enhanced phagocytosis. A more recent study confirmed that C1qRp is identical to CD93 protein, but failed to demonstrate a direct interaction between CD93 and C1q under physiological conditions. Recently it has been shown that CD93 is re-expressed during the late B cell differentiation and CD93 can be used in this context as a plasma cell maturation marker.

Function
CD93 was initially thought to be a receptor for C1q, but now is thought to instead be involved in intercellular adhesion and in the clearance of apoptotic cells. The intracellular cytoplasmic tail of this protein contains two highly conserved domains which may be involved in CD93 function. Indeed, the highly charged juxtamembrane domain has been found to interact with is_associated_with::moesin, a protein known to play a role in linking transmembrane proteins to the is_associated_with::cytoskeleton and in the remodelling of the cytoskeleton. This process appears crucial for both adhesion, migration and is_associated_with::phagocytosis, three functions in which CD93 may be involved.

In the context of late B cell differentiation, CD93 has been shown to be important for the maintenance of high antibody titres after immunization and in the survival of long-lived plasma cells in the bone marrow. Indeed, CD93 deficient mice failed to maintain high antibody level upon immunization and present a lower amount of antigen specific plasma cells in the bone marrow.