Two major theories concerning the development and differentiation of macrophages-the reticuloendothelial system proposed by Aschoff (1924) and the mononuclear phagocyte system developed by van Furth (1972)-are critically reviewed. Phylogenetically, mononuclear phagocytic cells (macrophages) develop in all animals; monocytes are not detected in invertebrates, and both macrophages and monocytes appear in vertebrates. The phylogenetic principle that the development and differentiation of macrophages precede those of monocytes during the evolutionary processes of animals applies to human and murine ontogeny of macrophages. In early ontogeny, macrophages develop from hematopoietic stem cells during yolk sac hematopoiesis, and the stage of monocytic cells is bypassed. Monocytic cells develop during hepatic hematopoiesis, and their development proceeds from the middle stage of ontogeny. In postnatal and adult life, macrophages are differentiated from macrophage precursor cells at different stages or through different pathways of differentiation. In addition to developing via the differentiation pathway of monocytic cells into macrophages, tissue macrophages develop from macrophage precursor cells at or before the stage of granulocyte/macrophage colony-forming cells, and some macrophage populations are derived from B lymphoid precursor cells. Dendritic cells are also derived from different precursor cells and are classified into myeloid dendritic cells, monocyte-derived dendritic cells, and lymphoid dendritic cells according to their precursor cell origin. Thus, macrophages and their related cells are believed to be differentiated from hematopoietic stem cells through multiple pathways. Finally, the roles of two major macrophage populations, Kupffer cells and monocyte-derived macrophages, in hepatic granuloma formation are analyzed by considering various mouse models.
In the past decades, significant progresses have been made in the field of research on Hodgkin's disease1, 2. Results obtained by the single cell analysis of Reed-Sternberg's cells on tissue sections, radically changed our understanding of this ever-debated disease3. Discovery of disturbed functions in some transcription regulatory factors also much clarified the pathophysiology of this disease. In this paper, a brief history and the molecular mechanisms of Hodgkin's disease so far understood will be reviewed.
Recent epidemiological studies reported changing trend of lymphoid neoplasia in the past few decades. Previous study of lymphomas from East Malaysia from 1981 to 1983 showed a pattern similar to other Asian countries, except for low incidence of peripheral T-cell lymphoma in Sarawak. Current study analyzed materials from 1996 to 1998, with the aim to elucidate possible change in disease pattern, if any, in Sarawak 15 years later. A total of 70 re-confirmed lymphoma cases were classified using WHO proposed list of lymphoid neoplasms. There were 61 (87.1%) non-Hodgkin's lymphoma (NHL) and 9 (12.9%) Hodgkin's lymphoma (HL), and NHL: HL ratio was 7:1. Diffuse large B-cell lymphoma was the most common subtype of NHL (62.3%). There was only one case of T-NHL, lymphoblastic type in the series. The number of Chinese patients in this series was relatively low. Overall EBV association was 8.2% in NHL (60% in Burkitt's type) and 33.3% in HL. Majority of the extra-nodal lymphoma was from gastrointestinal tract (14/35, 40.0%), of which 10 were from the intestines. In conclusion, current study showed extremely low incidence of T-NHL and low EBV association in both NHL and HL. In addition, intestinal lymphomas constitute a large proportion of extra-nodal cases.
The precise localization of the heat shock protein (HSP) 70 family on follicular dendritic cells (FDC) is not fully understood. The aim of the present study was to clarify the expression of both the inducible and constitutive 72/73kDa HSP 70 protein on FDC. The expression of heat shock protein (HSP) 72/73 on FDC in various lymphoid follicles was investigated. Immunohistochemically, HSP72/73 was detected on FDC in all the lymphoid tissues and showed extensive labeling of the light zone. Immunoelectron microscopy also confirmed that HSP72/73 was located not only diffusely in the cytoplasm but was also dotted in the nucleus of FDC. Although mantle zone lymphocytes and vascular walls in lymphoid follicles were faintly HSP72/73 positive, the germinal center lymphocytes were all negative. Finally, in situ hybridization demonstrated distinctive follicular expression of HSP70 mRNA. These data clearly indicate that HSP72/73 is ubiquitously expressed on FDC, although the significance of HSP 72/73 expression on FDC remains a mystery.
Using SL/Kh mice and AKR/J mice, which are animal models for spontaneous pre-B-cell leukemia and thymic lymphoma, respectively, we studied the protective influence of allogeneic bone marrow transplantation (BMT) and the induction of tolerance to Mls-1a, a host antigen. When BM cells from allogeneic C57BL/6 mice were used to reconstitute self-tolerance SL/Kh mice, these [B6→SL] chimeric mice survived for a longer time than non-treated SL or [SL→SL] syngeneic chimeras. These findings are compatible with results previously obtained for [B6→AKR] chimeras. In [B10. D2→SL] and [B10. D2→AKR] chimeras, Vβ6+ T-cells reactive to Mls-1a were eliminated 5 weeks after BMT. On the other hand, minor graft versus host reaction (GVHR) abrogated the clonal elimination of Vβ6+ T-cells in both [B10. D2→SL] and [B10. D2→AKR] chimeras. The cause of this abrogation was attributed to the early disappearance of Mls-1a-producing host T-cells in the GVHR chimeras. The cells responsible for the Mls-1a production were revealed to be mainly CD8+ CD44+ T-cells, by in vitro mixed lymphocyte reaction (MLR) and in vivo tolerance induction. The present findings indicate that host CD8+ CD44+ T-cells constitute the major source of Mls-1a antigens in the [Mls-1b→Mls-1a] BM chimera system.
A 58-year-old Japanese woman presented an eruption in the region of the back and the upper extremities, a subcutaneous nodule on the right breast, and a left cervical lymphadenopathy. The excision biopsy specimens, of a subcutaneous nodule and a lymph node, showed a vaguely nodular growth pattern comprising a small CD20+ IgD+ lymphocyte infiltrate around clusters of medium-sized or large CD3+ lymphoid cells, in which histological distinction between malignant lymphoma and reactive lymphoid hyperplasia was difficult. Southern-blot analysis revealed the presence of rearranged bands for the beta chain of the T-cell receptor, but not for the immunoglobulin heavy chain. The neoplastic cells were therefore identified to be of T-cell origin. This case represents an unusual cutaneous T-cell lymphoma with a prominent reactive population of B lymphocytes.
In this study, we reported five cases of CD5+ diffuse large B-cell lymphoma (DLBCL) which initially presented as bone marrow involvement without lymphadenopathy. The cases involved two males and three females, with an average age of 73.8 years. The patients had fever and showed general fatigue. Three of the five cases presented hepatosplenomegaly. Laboratory examination highlighted anemia, thrombocytopenia, presence or absence of leukopenia, hypoalbuminemia as well as a considerable elevation of serum lactate dehydrogenase, soluble IL-2R and ferritin. Bone marrow aspiration smears showed large-sized lymphoma cells, which were found to aggregate, and clot sections showed many clusters of lymphoma cells, which had a large and round or indented nucleus with vesicular chromatin and occasional small nucleoli. Mitotic rate was high. In the bone marrow clot section, whereas three cases exhibited a diffuse infiltration of the lymphoma cells (diffuse type), two cases exhibited a sinusoidal proliferation (intravascular type). Cytogenetic analysis showed many and complex abnormalities in all 3 cases examined. The lymphoma cells were positive for CD5, CD19, CD20, CD38, IgM, bcl-2 and bcl-6, while they were negative for CD3, CD10, CD23, CD30, cyclin D1 and TdT. In four cases, after a semi-nested PCR amplification of the immunoglobulin heavy chain (IgH) gene, a discrete band could be detected. All the cases exhibited an in-frame sequence and the frequency of somatic mutations ranged from 2.1 to 11.1% with no intraclonal diversity. These DLBCL may have derived from the same counterpart as CD5+ B-CLL. There were no differences in laboratory, immunological and molecular examination between the diffuse type and the intravascular type. Recurrences in the bone marrow and an aggressive clinical course were also observed in both types.