CD19 Bgp94, B4
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Lineage Restricted Molecule
Type 1 glycoprotein
B Cell
Dendritic Cell
Follicular Cell
90 / 90
95 / 95

Expression
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. 

Structure
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.

MOLECULAR MASS
Cell type Unreduced Reduced
B cells >120 kDa 95 kDa

POST-TRANSCRIPTIONAL MODIFICATION: No information.

POST-TRANSLATIONAL MODIFICATION

CD19 has 5 potential N-linked glycosylation sites and multiple serine/threonine and tyrosine phosphorylation sites.

Ligands
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
Molecule Comment
CD21 (CR2) The extracellular and transmembrane region of CD19 are required for association with CD21 (functional dissection of the CD21/CD19/TAPA-1/Leu-13 complex of B lymphocytes).
CD81 (TAPA-1) Member of the tetra-span family that associates directly with CD19 in a noncovalent manner within the membrane proximal extracellular region of CD19.
CD225 (Leu-13) Interferon inducible gene product that associates directly with CD81 and thereby associates with CD19 indirectly.
Lyn The extensive cytoplasmic domain of CD19 is reported to associate with Lyn, Lck, Fyn and phosphoinositide 3-kinase following tyrosine phosphorylation of CD19.
Fyn The extensive cytoplasmic domain of CD19 is reported to associate with Lyn, Lck, Fyn and phosphoinositide 3-kinase following tyrosine phosphorylation of CD19.
phosphoinositide 3-kinase (PI-3K) The extensive cytoplasmic domain of CD19 is reported to associate with Lyn, Lck, Fyn and phosphoinositide 3-kinase following tyrosine phosphorylation of CD19.
Vav  The tyrosine phosphorylated cytoplasmic domain of CD19 also associated with Vav (signaling through CD19 activates Vav/mitogen-activated protein kinase pathway and induces formation of a CD19/Vav/phosphatidylinositol 3-kinase complex in human B cell precursors), an association that is likely to biologically quite important.


 

Function
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.

BIOCHEMICAL ACTIVITY

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.

Comments
MOLECULAR INTERACTIONS -
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD19
Molecule Comment
Pax-5 (BSAP)

SUBSTRATES: No information.

ENZYMES WHICH MODIFY CD19: No information.

ADDITIONAL INSIGHTS

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
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgene 930P15391
MouseB45808P25918M62542
Antibodies
HIB19   View Reactivity
LT19   View Reactivity

Revised June 25, 2008


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