Immunobiology of chronic lymphocytic leukemia.
The majority of CLLs are of B lineage derivation with about 5 per cent of cases of T lineage. Although morphologically resembling the small peripheral blood B cell, by virtue of the expression of B cell restricted and associated cell surface antigens, B-CLLs are not the neoplastic counterparts of normal resting B cells. Similar to the peripheral blood B cell, B-CLLs express CD19, CD20, CD21, CD24, CD40, CD44, CD45R, and sIgM/D. However, unlike peripheral blood B cells, B-CLLs generally do not express C3b complement receptor, LFA-1, or CD22. In addition, B-CLLs express the T cell associated antigen CD5, and a number of antigens induced on normal B cells following in vitro activation (B5, Blast-1, CD23). These findings support the hypothesis that B-CLLs are the neoplastic counterparts of one or more unique subpopulations of normal B cells. Normal CD5+ B cells, which phenotypically resemble B-CLL, are present in fetal lymphoid tissues and in small numbers in adults. Moreover, normal CD5+ B cells are present in increased numbers in patients with autoimmune diseases and a subset of normal in vitro activated B cells phenotypically resemble B-CLL. Similar studies into the state of differentiation of T-CLL cells suggest that although most cases resemble normal activated T helper cells, a significant number are the neoplastic counterparts of natural killer cells. Recent studies have examined the function of B and T cells in B-CLL. Although controversial, these studies suggest that the in vitro response to mitogens and cytokines of B-CLL cells is abnormal. T cell proliferation in B-CLL is depressed due to an inability to produce sufficient T cell growth factor (IL-2) as well as a poor response to exogenous IL-2 possibly from ineffective IL-2 receptor expression. Purified populations of T helper and T suppressor cells demonstrate insufficient support of Ig production by normal B cells as well as excess suppression, respectively. These studies have further supported the previous hypothesis that the depressed cellular and humoral immunity in CLL is multifactorial with both abnormal B and T cell function.
Freedman
A S
AS
Department of Medicine, Harvard Medical School, Boston, Massachusetts.
D000943:Antigens, Differentiation / Q000032:analysis; D000951:Antigens, Neoplasm / Q000032:analysis; D014408:Biomarkers, Tumor / Q000032:analysis; D002454:Cell Differentiation; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology* / Q000473:pathology; D015461:Leukemia, Prolymphocytic, T-Cell / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation; D014411:Neoplastic Stem Cells / Q000276:immunology / Q000473:pathology; D010641:Phenotype
D000943:Antigens, Differentiation; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor