CD19

Assessments
Characteristics
Synonyms: B4, CVID3, Leu12. Nature: Transmembrane glycoprotein, a member of immunoglobulin superfamily. Gene and structure: Chromosomal localization 16 p11.2 Molecular weight 95 kDa. Occurrence and function: CD19 is expressed only on B-cells and follicular dendritic cells. It is a specific and sensitive marker of B-cells widely expressed from early pre-B stages, normal B-cells and normal plasma cells (staining is weaker than normal B-cells and a subpopulation may lack expression). It is considered a positive regulator of both intrinsic and stimulus-dependent pathways in B-lymphocytes. It is a part of B-cell Receptor Complexes (BCR) on the cell surface together with CD21, CD81 and CD225. The cytoplasmic domain serves as a signal transducing element amplifying B-lymphocyte signal by regulating Src family of tyrosine kinases. The development of B-cells is not influenced by CD19, but CD19 deficient mice show decrease in lymphocyte number and impairment of lymphocyte function as well as reduction in formation of germinal centres. Transgenic mice over-expressing CD19 show reciprocal phenotype with increase in peritoneal B-1 lymphocytes, increase B-cell proliferation, reduction of number of B-cells exiting bone marrow, reduced surface IgM, and elevated humoral immune responses. Small increase in CD19 density on the cell surface is associated with production of specific autoantibodies (against single- and double-stranded DNA, histone, rheumatoid factor and antinuclear antibodies). Abnormalities: Mutations of CD19 gene are found in some cases of common variable immunodeficiency syndrome (CVIS) in humans.
Neoplasms
CD19 is found on majority of B-cell neoplasms with some exceptions. Follicular lymphoma regardless of grade is CD19 positive in 48-79% of the cases while around 6% of the cases are reported negative. Large B-cell lymphoma is positive in 24-50% of the cases, another 14% are negative. T-cell rich B-cell lymphomas show low expression in 40% and negative staining in 30%. Chronic lymphocytic B-cell leukaemia is positive in 36% of the cases. Only 13% of marginal zone B-cell lymphomas are positive. CD19 is generally weakly expressed in B-cell prolymphocytic leukaemia, splenic lymphoma with villous lymphocytes and mantle cell lymphoma. The CD19 reactivity patterns differ from those of CD20 in several B-cell lesions: In plasma cells neoplasms with t(11;14) the expression of CD19 and CD20 is mutually exclusive, the majority of cases are CD20+ while only a small fraction of these tumours expresses CD19. Hodgkin and Reed-Sternberg cells in classical Hodgkin Lymphoma are generally CD19 negative, while around 40% are positive for CD20. Lymphocytic-Histiocytic (L&H) cells of nodular lymphocytic predominant Hodgkin lymphoma are negative, while staining for CD20 is positive as a rule. Post-transplant lympho-proliferative disease is CD19 negative, while expression of CD20 is usually present. CD20 is strongly expressed in T-cell rich B-cell lymphoma, B-cell prolymphocytic leukaemia, splenic lymphoma with villous lymphocytes and mantle cell lymphoma as opposed to a weaker CD19 reaction mentioned above. The expression of CD19 is diminished in about 1/3 of cases of all B-cell lymphomas when compared with normal B-cells. This may be helpful in subclassification of lymphomas, mostly in flow cyto-photometric studies where differences in expression are easiest to detect, but may be have also practical application on tissue sections. Follicular dendritic cell tumours are reported CD19 positive. CD19 is also expressed on blasts in acute myeloid leukaemia (AML), most often (>50%) in cases with t(8;21).
Application
CD19 is useful in identification of B-cell lineage of majority of B-cell neoplasms but appears to be less useful in subclassifying of B-cell neoplasms in histological material. It appears to be potentially useful additional marker of follicular dendritic cell tumours. Similarly to CD20 it may also serve as a potential target for antibody-based immunotherapy.
Controls
Tonsil and appendix are both appropriate controls: The mantle zone B-cells, the germinal centre B-cells and the follicular dendritic cells must show a strong staining reaction. Weakly positive normal plasma can be seen. No other cells should stain.
Selected references
Bacchelli C, Buckridge S, Thrasher AJ, Gaspar HB. Translational mini-review series on immunodeficiency: molecular defects in common variable immunodeficiency. Clin Exp Immunol. 2007;149(3):401-9.Bataille R, Jégo G, Robillard N, Barillé-Nion S, Harousseau JL, Moreau P, Amiot M, Pellat-Deceunynck C. The phenotype of normal, reactive and malignant plasma cells. Identification of "many and multiple myelomas" and of new targets for myeloma therapy. Haematologica. 2006;91(9):1234-40. Fujimoto M, Poe JC, Hasegawa M, Tedder TF. CD19 regulates intrinsic B lymphocyte signal transduction and activation through a novel mechanism of processive amplification. Immunol Res. 2000;22(2-3):281-98. Ginaldi L, De Martinis M, Matutes E, Farahat N, Morilla R, Catovsky D. Levels of expression of CD19 and CD20 in chronic B cell leukaemias. J Clin Pathol. 1998;51(5):364-9. Ishikawa H, Tsuyama N, Mahmoud MS, Fujii R, Abroun S, Liu S, Li FJ, Kawano MM. CD19 expression and growth inhibition of tumours in human multiple myeloma. Leuk Lymphoma. 2002;43(3):613-6. Masir N, Marafioti T, Jones M, Natkunam Y, Rüdiger T, Hansmann ML, Mason DY. Loss of CD19 expression in B-cell neoplasms. Histopathology. 2006 Feb;48(3):239-46. Ord DC, Edelhoff S, Dushkin H, Zhou LJ, Beier DR, Disteche C, Tedder TF. CD19 maps to a region of conservation between human chromosome 16 and mouse chromosome 7. Immunogenetics. 1994;39(5):322-8. Pallesen G, Myhre-Jensen O. Immunophenotypic analysis of neoplastic cells in follicular dendritic cell sarcoma. Leukemia. 1987;1(7):549-57. Tedder TF, Isaacs CM. Isolation of cDNAs encoding the CD19 antigen of human and mouse lymphocytes. A new member of immunoglobulin superfamily. J.Immunol.1989;143(2):212-7. Yang W, Agrawal N, Patel J, Edinger A, Osei E, Thut D, Powers J, Meyerson H. Cytometry B Clin Cytom. 2005;63(1):28-35.Diminished expression of CD19 in B-cell lymphomas.
29.06.12 - JK/MV/LE