Lymphoproliferative disorders (LPD)comprise a heterogeneous group of diseases characterized by uncontrolled production of lymphocytes that cause monoclonal lymphocytosis, lymphadenopathy and bone marrow infiltration.They Typically occur in people who have a compromised immune system with highly variable clinical course.
Lymphoproliferative disorders are immunomorphologically and clinically heterogeneous. The two major types of lymphocytes are B cells and T cells, which are derived from pluripotent hematopoietic stem cells in the bone marrow.
Lymphoproliferative disorders include; Follicular lymphoma, chronic lymphocytic leukemia, acute lymphoblastic leukemia, hairy cell leukemia, Hemophagocytic lymphohistiocytosis (HLH), B-cell lymphomas, T-cell lymphomas, multiple myeloma, Waldenström's macroglobulinemia, Wiskott Aldrich syndrome, Langerhans cell histiocytosis (LCH), Lymphocyte-variant hypereosinophilia, Pityriasis Lichenoides, post-transplant lymphoproliferative disorder, autoimmune lymphoproliferative syndrome (ALPS), Lymphoid interstitial pneumonia, Epstein Barr virus associated lymphoproliferative diseases, Castleman disease and X-linked lymphoproliferative disease.
Many patients are asymptomatic at the time of first presentation, with the diagnosis being made as an incidental finding after a routine medical examination or blood test, for example, complete blood count (CBC).
Definitive diagnosis is made on the characteristic lymphocyte morphology and immunophenotype usually from samples of peripheral blood ,bone marrow samples or lymph nodes.
The membrane receptor proteins (CD19, CD81, CD21 (complement receptor type2) and Leu-13(CD225)), form a complex (CD19 complex) on human B lymphocytes that has costimulatory activity for the antigen receptor, membrane IgM(mIgM) .The complex is unique among known membrane protein complexes of the immune system because its components represent different protein families, and can be expressed individually.
The biochemical mechanism by which the complex costimulates is not understood.CD19 has been shown to be a major substrate of a protein tyrosine kinase activated by mIgM, and tyrosine phosphorylated CD19 binds phosphatidylinositol 3-kinase (PI3-kinase), an enzyme that is required for the cellular activating effects of certain receptor tyrosine kinases. Thus, several biochemical pathways may be triggered by the CD21/CD19/CD81/CD225 complex that relate to its role in amplifying the response of B cells to antigen.
Multiple biologic effects of the CD21/CD19/ CD81/CD225 complex may reflect the discrete actions of individual components, each of which is a member of a distinct protein family: CD21 of the regulators of complement activation family; CD19 of the Ig superfamily;and CD81 of the tetraspan family of membrane proteins and is an important regulator of B-cell signaling. CD225 of Interferon-induced transmembrane protein (IFITM) family.
Although CD19 function may be elicited following its potential binding to an as yet unidentified ligand, C3d binding to CD21 supplies an already characterized ligand for the CD19 complex, thereby linking complement immune responses and the generation of immunological activation and B cell function.
Ligation of members of the CD19 complex initiates a cascade of biological responses that can modulate signal transduction through the B cell Ag-receptor complex and other cell surface receptors. So it may help in understanding the signal transduction pathways through this complex.
