|Molecule Type||Antigen Expression||Molecular Weight|
Min / Max
|Lineage Restricted Molecule|
Type 1 glycoprotein
|90 / 90|
95 / 95
|CD19 is expressed on the earliest B lineage cells up to B cell blasts but is lost on plasma cells. Expression is also in malignant B cells and follicular dendritic cells. |
|MOLECULAR FAMILY NAME: Belongs to the immunoglobulin supergene family.|
CD19 is a single-pass type-1 glycoprotein. It contains a 288 aa extracellular domain which is heavily glycosylated and contains 2 Ig-like C2-type domains separated by a 67 aa small potentially disulphide-linked domain and has 5 potential N-linked glycosylation sites, a transmembrane domain and a 240 aa cytoplasmic domain which is related to Epstein-Barr virus proteins and has multiple tyrosine phosphorylation sites on Ser/Thr and Tyr residues. The extracellular domain has extensive sequence similarity to the β-subunits of Shiga-like toxin of E. coli and potentially binds CD77 (Shiga-toxin receptor and marker of germinal center B cells). Phosphorylation of tyrosine residues in the cytoplasmic domain YEXM motifs creates binding motifs for the SH2 domains of phosphatidylinositol 3-kinase (PI-3k) and non-receptor protein tyrosine kinases.
POST-TRANSCRIPTIONAL MODIFICATION: No information.
CD19 has 5 potential N-linked glycosylation sites and multiple serine/threonine and tyrosine phosphorylation sites.
|CD19 is a component of the CD19/CD21/CD81/leu-13 signaling complex. The CD19/CD21 interaction has a 1:1 stoichiometry and is mediated by both extracellular and transmembrane regions of CD19, whereas the CD19/CD81 interaction involves the CD19 extracellular region only. CD19 links this complex to cytoplasmic signal transduction pathways. |
LIGANDS AND MOLECULES ASSOCIATED WITH CD19
|CD19 interacts with CD77 playing a role in germinal center formation, B-cell homing and apoptosis. CD19 is a critical signal transduction molecule that regulates B lymphocyte development, activation, and differentiation. The CD19/CD21/CD81/Leu-13 signaling complex modulates the threshold for the BCR. The functions of CD81 and CD225 (Leu-13), the expression of which are not restricted to B cells, are not clear. However CD21 complement receptor 2 binds fragments of C3 that have been co-valently attached to glycoconjugates by complement activation. This enables CD19, plus associated intracellular signaling molecules, to be crosslinked to the B cell antigen receptor after pre-immune recognition of an immunogen by the complement system, thus reducing the number of B cell receptor molecules which must be ligated to enable B cell activation. This mechanism may be particularly important for the B cell during the primary immune response, prior to affinity maturation, when the low affinity B cell antigen receptor must respond to low concentrations of antigen. This co-receptor role for CD19 is supported by data from CD19 knockout and transgenic mice. CD19 null mice have decreased numbers of B cells, decreased mitogenic responses, low germinal center formation, and decreased humoral immune responses to T cell-independent type 1 and T cell dependent antibodies. CD19 antibodies increase cytoplasmic calcium levels in B cells and block proliferation of resting B cells in response to various stimuli except PMA.|
CD19 is involved in signal transduction. Ligation of CD19 alone increases intracellular Ca2++. CD19 monoclonal antibody HD37 inhibits anti-immunoglobulin-induced B cell activation and proliferation. Coligation of CD19 to membrane immunoglobulin augments the increase in Ca2++ and inositol trisphosphate induced by the antigen receptor, the CD19 complex of B lymphocytes. The membrane IgM complex can enhance activation of phospholipase C by a protein tyrosine kinase-dependent pathway.
DISEASE RELEVANCE AND FUNCTION OF CD19 IN INTACT ANIMAL
CD19-deficient mice have decreased numbers of conventional and substantially decreased numbers of B-1 lineage B cells. CD19-deficient B cells have decreased proliferative responses to all mitogens. CD19-deficient mice have decreased humoral immune responses to T cell-independent type-1 and T cell-dependent antigens. Some investigators find that CD19-deficient mice have augmented responses to a T cell-independent type-2 antigen. However there is no complete agreement on the requirement for CD19 in a type-2 T-independent antibody response, or for the in vitro proliferation of B cells induced by ligating mIg. Germinal center formation is significantly reduced in CD19-deficient mice. B lymphocytes from human-CD19 transgenic mice that overexpress CD19 generate increased responses to transmembrane signaling. Mice that overexpress CD19 have dramatically augmented numbers of B-1 cells and augmented production of autoantibodies.
|MOLECULAR INTERACTIONS -|
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD19
SUBSTRATES: No information.
ENZYMES WHICH MODIFY CD19: No information.
CD19 is a response regulator that plays a dominant role in establishing signaling thresholds for antigen receptors and other surface receptors on B lymphocytes.
Database accession numbers
Revised June 25, 2008