Kikue Iwamasa

Abnormal Immune Function of Hemopoietic Cells from Alymphoplasia ( aly ) Mice, a Natural Strain with Mutant NF-κB-Inducing Kinase

Alymphoplasia (aly) mice, a natural strain with a mutant NF-κB-inducing kinase (NIK) gene, manifest a unique phenotype; they lack lymph nodes and Peyer’s patches, have a disturbed spleen architecture, and exhibit defects in both Ab and cellular immune responses. Although a stromal defect caused by impaired lymphotoxin-β receptor signaling accounts for their abnormal lymphoid organogenesis, the exact mechanisms underlying the development of immunodeficiency in aly mice are poorly understood. We therefore investigated the contribution of hemopoietic cells with the aly NIK mutation to the development of immunodeficiency. Transfer of aly/aly bone marrow cells into aly/+ mice resulted in poorly developed B cell follicles and lack of support for the development of germinal centers and isotype switching, indicating that the hemopoietic cells of aly mice contain an autonomous defect. However, follicular dendritic cell clusters were maintained in the spleens of these bone marrow chimeras, suggesting that the lack of follicular dendritic cell clusters in aly mice is probably due to the stromal defect. The aly mice lacked marginal zone B cells in their spleens, and aly/aly B cells showed an impaired proliferative response after in vitro stimulation. IL-2 production by activated T cells was also impaired. By contrast, the dendritic cells of aly mice exhibited grossly normal development and function. Supporting the concept of an autonomous cell defect, Rel protein expression was altered in aly/aly spleens. Thus, the aly NIK mutation affects hemopoietic cell function in an intrinsic fashion and, together with the stromal defect, may contribute to the development of immunodeficiency in aly mice.

Phenotypic and genotypic analysis of chronic myelogenous leukaemia with T lymphoblastic and megakaryoblastic mixed crisis

A case of blast crisis in chronic myelogeneous leukaemia (CML) in which two distinct cell lineages were involved is presented. The phenotype of blasts in lymph nodes was T11 (CD2)+, Ia+, TdT+, suggesting T cell lineage. On the other hand, blasts in bone marrow and peripheral blood expressed platelet glycoprotein IIb/IIIa complex on their surface, suggesting megakaryocyte lineage. Cytogenetic analysis of lymph node and bone marrow cells revealed the abnormalities. inv(7) (p15q34) and t(1;3) (q23;q21), respectively, as well as the presence of the Ph1 chromosome in both cell types. Rearrangement of the T cell receptor β‐chain gene was detected in lymph node blasts, although blast cells in peripheral blood showed a germ line configuration. The involvement of T cell and megakaryocyte lineages in the blast crisis phase of CML was confirmed in our phenotypic and genotypic analysis, and the pathogenic association between blast crisis lineages and the additional chromosome abnormalities present is discussed.

BehÇet’s disease associated with myelodysplastic syndrome with elevated levels of inflammatory cytokines

Abstract We report the case of a 56-year-old Japanese woman with Behçet’s disease and myelodysplastic syndrome (MDS), who had a history of episodic high-grade fever, recurrent oral and genital ulcers, and erythema nodosum, during a 13-year period from 1989 to 2002. Bone marrow aspirates obtained in January 1995 showed refractory anemia with trisomy 8, a subtype of MDS. Her serum levels of soluble interleukin-2 receptor (IL-2R), interferon-γ, IL-1β, IL-6, IL-8, and granulocyte–macrophage colony stimulating factor in the active state were higher than those in the inactive state, whereas those of tumor necrosis factor-α and IL-10 did not increase even in the active state. In this case, it was speculated that a T-cell immune response might have been involved in the disease pathogenesis, and that the repeated febrile episodes might have been a manifestation of neutrophil hyperfunction induced by increased serum levels of inflammatory cytokines.

Multiphenotypic Lymphoma with Rearrangements of the T Cell Receptor Beta Chain and Gamma Chain Genes

A case of chemotherapy-resistant non-Hodgkins lymphoma simultaneously expressing T cell (CD7)-, B cell (CD19)- and myeloid (CD13, CD33)-associated surface antigens is presented. Cytochemical analysis revealed that the lymphoma cells were positive for terminal deoxynucleotidyl transferase, but negative for myeloperoxidase and esterase. Rearrangements of both the T cell receptor beta chain and gamma chain genes were observed, but the immunoglobulin genes showed a germ line configuration. The rearrangement was not detected within the breakpoint cluster region on chromosome 22. These findings are considered to represent aberrant expressions of the B cell- and myeloid-associated antigens in early-stage T cell lineage lymphoma cells.

REARRANGEMENT OF THE bcr GENE IN CHRONIC MYELOGENOUS LEUKAEMIA WITH T LYMPHOBLASTIC AND MEGAKARYOBLASTIC MIXED CRISIS

1 1 8 M 2 75F 3 2 0 F 4a 16M 4b 1 7 M 5 70F 6 37M 7 6 6 M 8a 2 7 F 8b 2 7 F 9 75F 30 24M 11 3 6 F 12 25M 19 40 33 17 50 30 35 16 10 4 70 14 70 19 -8.7 -28.2 -9.8 32.2 12.7 36.8 -23.7 6.3 6.0 13.0 -12.0 9.0 -28.0 6.9 not compete for the same receptor site on the megakaryocyte membrane or that their cellular targets are at different stages of differentiation. Should the latter be the case, it is logical to suggest that the thrombopoietic inhibitory activity might influence the early megakaryocytic progenitors (CFU-M) with the consequent depression of their cloning capacity, as the thrombopoietic stimulatory activity exerts its effect on the nonproliferative pool of terminally differentiating megakaryocytes (Hoffman et al, 1983). So the poor megakaryocyte colony formation by bone marrow progenitors reported by Juvonen et a1 and the presence of thrombopoietic inhibitory activity in 5 7% of the RA sera found in our study may have some relation and could indicate the presence of a wide spectrum of disorders of megakaryocytopoiesis and thrombopoiesis in patients with myelodisplastic syndromes.