• B4

MAJOR LINKS FOR CD19  

• NCBI LocusLink Record: 930
• Mendelian Inheritance in Man (OMIM): 107265
• SwissProt annotated protein record: P15391

• 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. (Pezzutto A et al. 1987)**
• 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. (Carter RH et al. 1991)**

CELLULAR FUNCTION OF CD19  

• CD19 is a critical signal transduction molecule that regulates B lymphocyte development, activation, and differentiation

DISEASE RELEVANCE OF CD19 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 not 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

• Families in which CD19 is a member
  • CD19-->immunoglobulin supergene family

MOLECULAR STRUCTURE OF CD19  

• About 280 amino acid extracellular domain that contains two C2-type Ig-like domains separated by a smaller potentially disulfide-linked domain
• About 240 amino acid cytoplasmic domain

MOLECULAR MASS OF CD19  

POST-TRANSCRIPTIONAL MODIFICATION OF CD19   - None

POST-TRANSLATIONAL MODIFICATION OF CD19  

• Five potential N-linked glycosylation sites
• Multiple serine/threonine and tyrosine phosphorylation sites

SUBSTRATES FOR CD19   - No information

ENZYMES WHICH MODIFY CD19   - No information

LIGANDS FOR CD19 AND MOLECULES ASSOCIATED WITH CD19  

• Expressed on B cells and follicular dendritic cells
• B lineage expression from the earliest recognizable B-lineage cells (early Ig gene rearrangements) to B cell blasts
• Lost on maturation to plasma cells
• Malignant B cells

• CD19 is a response regulator that plays a dominant role in establishing signaling thresholds for antigen receptors and other surface receptors on B lymphocytes

SELECTION OF OTHER CD19-SPECIFIC REFERENCE MAB  

REVIEWS

1. Tedder TF,Zhou LJ,Engel P The CD19/CD21 signal transduction complex of B lymphocytes. Immunol Today 1994 15:437 PubMed

PRIMARY CITATIONS

2. Bradbury LE,Kansas GS,Levy S,Evans RL,Tedder TF The CD19/CD21 signal transducing complex of human B lymphocytes includes the target of antiproliferative antibody-1 and Leu-13 molecules. J Immunol 1992 149:2841 PubMed

3. Carter RH,Fearon DT CD19: lowering the threshold for antigen receptor stimulation of B lymphocytes. Science 1992 256:105 PubMed

4. Carter RH,Tuveson DA,Park DJ,Rhee SG,Fearon DT The CD19 complex of B lymphocytes. Activation of phospholipase C by a protein tyrosine kinase-dependent pathway that can be enhanced by the membrane IgM complex. J Immunol 1991 147:3663 PubMed

5. Engel P,Zhou LJ,Ord DC,Sato S,Koller B,Tedder TF Abnormal B lymphocyte development, activation, and differentiation in mice that lack or overexpress the CD19 signal transduction molecule. Immunity 1995 3:39 PubMed

6. Matsumoto AK,Kopicky-Burd J,Carter RH,Tuveson DA,Tedder TF,Fearon DT Intersection of the complement and immune systems: a signal transduction complex of the B lymphocyte-containing complement receptor type 2 and CD19. J Exp Med 1991 173:55 PubMed

7. Nadler LM,Anderson KC,Marti G,Bates M,Park E,Daley JF,Schlossman SF B4, a human B lymphocyte-associated antigen expressed on normal, mitogen-activated, and malignant B lymphocytes. J Immunol 1983 131:244 PubMed

8. Pezzutto A,Dorken B,Rabinovitch PS,Ledbetter JA,Moldenhauer G,Clark EA CD19 monoclonal antibody HD37 inhibits anti-immunoglobulin-induced B cell activation and proliferation. J Immunol 1987 138:2793 PubMed

9. Rickert RC,Rajewsky K,Roes J Impairment of T-cell-dependent B-cell responses and B-1 cell development in CD19-deficient mice. Nature 1995 376:352 PubMed

10. Sato S,Steeber DA,Tedder TF The CD19 signal transduction molecule is a response regulator of B- lymphocyte differentiation. Proc Natl Acad Sci U S A 1995 92:11558 PubMed

11. Steeber DA,Green NE,Sato S,Tedder TF Lyphocyte migration in L-selectin-deficient mice. Altered subset migration and aging of the immune system. J Immunol 1996 157:1096 PubMed

12. Tedder TF,Isaacs CM Isolation of cDNAs encoding the CD19 antigen of human and mouse B lymphocytes. A new member of the immunoglobulin superfamily. J Immunol 1989 143:712 PubMed

13. Tuveson DA,Carter RH,Soltoff SP,Fearon DT CD19 of B cells as a surrogate kinase insert region to bind phosphatidylinositol 3-kinase. Science 1993 260:986 PubMed

14. Weng WK,Jarvis L,LeBien TW 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. J Biol Chem 1994 269:32514 PubMed

15. Zhou LJ,Smith HM,Waldschmidt TJ,Schwarting R,Daley J,Tedder TF Tissue-specific expression of the human CD19 gene in transgenic mice inhibits antigen-independent B-lymphocyte development. Mol Cell Biol 1994 14:3884 PubMed

WWW RESOURCES

Portions copyright by Garland Press and by the International Workshops on Human Leukocyte Differentiation Antigens; used with permission

Modified 10/14/99   mpr@mail.nih.gov