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F Caligaris-Cappio

Publications and source records attributed to F Caligaris-Cappio.

At least 91 records · Page 5Linked to original sources

Cytoskeleton organization is aberrantly rearranged in the cells of B chronic lymphocytic leukemia and hairy cell leukemia.

The organization of actin-containing microfilaments and vimentin-containing intermediate filaments has been investigated in B chronic lymphocytic leukemia (B-CLL), hairy cell leukemia (HCL), and normal B cells cultured in vitro under basal conditions and after induction with 12-O-tetradecanoyl-phorbol-13-acetate (TPA). In uninduced B-CLL cells, F-actin was predominantly associated with dot-shaped structures scattered over the ventral membrane representing spotty close contact adhesion sites analogous to "podosomes" described in other cell types. On TPA induction, podosomes became clustered in sharply defined areas sitting in the cell center beneath the nucleus. In some cells, long actin-containing protrusions appeared. In HCL cells, F-actin was associated with thin microvilli responsible for the "hairy" appearance; occasional cells showed scattered podosomes. On TPA induction, HCL cells sprouted long dendritic processes rich in submembraneous F-actin, which made intertwined networks. Therefore, in both B-CLL and HCL cells, adhesion structures were present and the capacity for adhesion in vitro was marked, which might explain some peculiar clinical features of the diseases. Adhesion structures and adhesive properties never appeared in normal B cells. These data further support the notion that B-CLL and HCL, although clinically different, may share common biological features and suggest that in these disorders, cytoskeleton modifications may represent a hallmark of transformation.

Actin Cytoskeleton↗

Immunohistochemical demonstration of follicular dendritic cells in bone marrow involvement of B-cell chronic lymphocytic leukemia.

Using a sensitive immunohistochemical technique and a specific monoclonal antibody (RFD-3), follicular dendritic cells (FDC) have been demonstrated in a significant proportion (6/12) of bone marrow samples from patients with nodular marrow involvement of B-cell chronic lymphocytic leukemia (B-CLL). In all cases with "packed marrow" involvement and advanced stages of disease the FDC were absent. As these accessory cells are normally present only in the lymph nodes, their presence in the bone marrow is in accord with the view that B-CLL might be the malignancy of an immature subpopulation of lymph node lymphocytes that invade the bone marrow.

Adult↗

Functional and molecular characterization by the CB04 monoclonal antibody of a cell surface structure exerting C3-complement receptor activity.

CB04 monoclonal antibody which reacts with an epitope of a surface molecule expressed on human monocytes has been elicited using peripheral blood lymphocytes as immunizer. The characterization of the monoclonal antibody examined at the phenotypic, molecular, and functional levels indicates that the CB04 antibody defines a structure present on monocytes, tissue macrophages, B cells, polymorphonucleates, and erythrocytes. The molecular weight (220 kD), the tissue distribution in health and disease conditions, and the involvement in relevant biological processes indicate that the CB04 structure is the receptor for the C3b fragment of the complement. The binding of the antibody to the cell surface induces inhibition of the C3bi receptorial function.

Animals↗

Murine monoclonal antibodies as probes for the phenotypical, functional, and molecular analysis of a discrete peripheral blood lymphocyte population exerting natural killer activity in vitro.

Two monoclonal antibodies (AB8.28 and A10) reacting with large granular lymphocytes were extensively studied and characterized. The two peripheral blood lymphocyte subsets positive for the expression of AB8.28 and A10 determinants were isolated by cell sorting and the phenotype analyzed using a panel of anti-lymphocyte reagents. Both subsets displayed the characteristics of "null cells." Moreover, these subsets encompassed a significant amount of the natural killer activity, since preparations of peripheral blood lymphocytes deprived of AB8.28+ and A10+ cells showed a remarkable reduction of such activity. The analysis of the distribution of the AB8.28 and A10 epitopes has been carried out using a variety of cells, i.e., normal tissues, tumor cells, established cell lines, and preparations obtained from patients with different leukemic disorders. The structure bearing the epitopes recognized by the two monoclonal antibodies was characterized immunologically (immunoprecipitation, SDS-PAGE analysis, immunomodulation, and competition with other antibodies) and by various functional assays. On the basis of inhibition tests, the AB8.28 molecule seems to be related functionally and/or structurally with the IgG Fc receptor. By contrast, the A10 structure does not share this activity and so far has eluded any precise biological characterization.

Antibodies, Monoclonal↗

A possible pathogenetic role of cationic proteins (CP) released by stored granulocytes in the development of pulmonary infiltrates after granulocyte transfusions.

The cationic protein (CP) content of polymorphonuclear neutrophils (PMN) prepared for transfusion is depleted after storage. The supernatants from these PMN have in vitro a PMN aggregating activity which is abolished by the preabsorption with a specific rabbit anti-human PMN CP serum. Furthermore, when the supernatants stored for few hours were injected into New Zealand White rabbits, a marked sequestration of PMN took place in the lung microvascular bed. It is suggested that PMN storage per se can cause the release of intracellular mediators of possible pathogenetic importance in the development of the pulmonary infiltrates observed after PMN transfusions.

Adult↗

Identification of malignant plasma cell precursors in the bone marrow of multiple myeloma.

Precursors of plasma cells were studied in the bone marrow of 28 patients with multiple myeloma, plasma cell leukemia, and benign monoclonal gammopathy. Pre-B and B cell populations were analyzed with anti-B monoclonal antibodies corresponding to the clusters standardized at the Leucocyte Typing Workshops in Paris and Boston (CD9, CD10, CD19-22, CD24). In advanced forms of plasma cell malignancies, such as cases of multiple myeloma in stages II and III and of plasma cell leukemia, some cells of lymphoid morphology expressed common acute lymphoblastic leukemia antigen (CALLA, CD10) and HLA-DR, but contained no detectable terminal deoxynucleotidyl transferase enzyme. These CALLA+ cells were absent in benign monoclonal gammopathies. In multiple myeloma, the CALLA+ cells were negative for surface and cytoplasmic immunoglobulins (Ig), and, unlike CALLA+, terminal deoxynucleotidyl transferase (TdT+) pre-B cells in the normal bone marrow also failed to react with antibodies to B cell-associated antigens such as CD9, CD19, CD22, and CD24. The CALLA+, Ig- cells could be regarded as preplasmacytic since, after having been separated and stimulated with the phorbol ester 12-0-tetradecanoyl-phorbol-13 acetate in vitro, they transformed into plasma cells and synthesized the same heavy and light chains as myeloma cells.

Adult↗

HLA-Dr+ T cells of the Leu 3 (helper) type infiltrate the kidneys of patients with systemic lupus erythematosus.

The lineage and distribution of mononuclear cells infiltrating the kidneys of patients with systemic lupus erythematosus (SLE) have been investigated in cryostat tissue sections of biopsies from 11 patients. The use of heterologous antisera and monoclonal antibodies has revealed that: B lymphocytes and plasma cells are virtually absent in SLE kidney specimens; The vast majority of mononuclear cells which infiltrate the interstitium are activated (HLA-Dr+) T cells (Leu 4+) presenting the helper (Leu 3+) phenotype; T cells are absent in the glomeruli, where HLA-Dr+, SIgM-, Leu 4- elements with a macrophage like appearance can be observed.

Adult↗

Phorbol ester induces abnormal chronic lymphocytic leukemia cells to express features of hairy cell leukemia.

We have investigated the relationship between chronic lymphocytic leukemia (CLL), hairy cell leukemia (HCL), and different normal B cell subsets: Mrbc+, T1+ and slgM+ tonsil cells; germinal center; mantle zone; and peripheral blood B lymphocytes. Both malignant and normal cells were incubated in vitro with the phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate (TPA) for 72 hours and the morphology, cytochemical profile, and surface markers were evaluated. The results show that CLL cells TPA-induced become indistinguishable from HCL by four independent criteria: the morphology; the cytoplasmic tartrate resistant acid phosphatase (TRAP) enzyme activity; the membrane positivity with anti-Leu M5 (SHCL3); and anti-Tac monoclonal antibodies which, in the uninduced state, react only with HCL. The features of TRAP and Tac positivity are also expressed (though in variable degree) by different normal B cell populations activated with TPA or pokeweed mitogen (PWM). It is concluded that HCL might represent an aberrantly activated variant of CLL (or of a CLL-related disorder).

Acid Phosphatase↗

Lineage relationship of chronic lymphocytic leukemia and hairy cell leukemia: studies with TPA.

The tumor promoting agent TPA (phorbol ester; 1.6 X 10(-8)M) was used to induce the differentiation in vitro of B-chronic lymphocytic leukemia (B-CLL) cells from 14 untreated patients. The uninduced phenotype was SIg+, Mrbc+, RFT-1+, RFA-4-, FMC7-. After 72 h incubation with TPA, B-CLL cells became RFA-4+, FMC7+ and lost the capability of Mrbc rosetting. Large proportions of the "induced" cells also showed morphological and ultrastructural changes, such as undulating membranes and bleblike protusions and became strongly positive for tartrate resistant acid phosphatase (TRAP+) and also contained cytoplasmic immunoglobulins. These features are very similar to the features of hairy cell leukemia (HCL). These observations confirm previous clinical findings that B-CLL and HCL are related disorders of the B lineage. The development of "hairy" features in induced B-CLL and in HCL seems to be a malignancy-associated feature because the Mrbc+ normal B cells (B-CLL-equivalent cells) isolated from tonsil also develop TRAP positivity but no membrane aberrations.

B-Lymphocytes↗

Characterization of a murine monoclonal antibody specific for human early lymphohemopoietic cells.

This paper summarizes the results of the characterization of A10, a murine monoclonal antibody which recognizes an epitope not restricted to cells of a definite lineage, but which seems to be specific for an early differentiation antigen present on precursors of circulating T and B cells. The structure recognized by the A10 monoclonal antibody, although strikingly structurally similar to the HLA-A,B,C complex, is immunologically different both from histocompatibility antigens and from beta 2 microglobulin. Furthermore, the distribution of the A10 antigen is analyzed in different cell and tissue samples, both in health and disease conditions.

Animals↗

B-chronic lymphocytic leukaemia patients with stable benign disease show a distinctive membrane phenotype.

The circulating B cells of 98 patients with B-CLL were analysed with a panel of conventional markers and monoclonal antibodies including RFA-1 and RFA-4. A subgroup of patients was defined with a distinctive double membrane marker phenotype (RFA-1+, RFA-4+). These patients showed features of clinical stability. Their physical signs, haematological features and lymphocyte counts remained unchanged for 5-10 years: therefore, the RFA-1+, RFA-4+ membrane phenotype appears to identify a subgroup of B-CLL patients with a particularly non-progressive disease.

Aged↗

Generation and characterization of murine monoclonal antibodies against HLA Class II molecules.

HLA Class II antigens (human la) are coded by Major Histocompatibility Complex and play important biological roles in health and disease. In this report we describe the generation and characterization of nine murine monoclonal antibodies (MoAbs) specific for determinants localized on the human la molecules. The reactivity of these MoAbs inferred from serological analysis along with the data obtained from biochemical characterization of the target structures allowed a classification of these reagents as monomorphic and polymorphic. Two monomorphic MoAbs, identifying different subsets of human la molecules, were studied in detail.

Animals↗

Functional behaviour and immunological phenotype of circulating B lymphocytes in multiple myeloma. Studies with pokeweed mitogen.

Peripheral blood B lymphocytes, depleted of adherent cells, from 10 patients with multiple myeloma were cultured in the presence of PWM with autologous or donor T lymphocytes. The results show that: (1) co-cultures with allogeneic T lymphocytes produced more plasma cells than those with autologous ones; (2) the kappa/lambda ratio overlapped the values obtained in normal controls, irrespective of the light chain produced by the neoplastic plasma cells and (3) the immunological phenotype of plasma cells obtained from PWM stimulated peripheral B cells (RFA2+, RFA3+, A10+) was clearly different from that one of myelomatous plasma cells (RFA2-, RFA3-, A10+). These data confirm the T cell imbalance already seen in myeloma patients; moreover they show that PWM responsive B cell are functionally normal and phenotypically different from bone marrow myeloma cells. These results support the view that most of the peripheral B lymphocytes, previously identified as monoclonal are in fact normal cells bearing adherent monoclonal Ig molecules.

Antibodies, Monoclonal↗

Normal equivalent cells of B cell malignancies: analysis with monoclonal antibodies.

Immunoglobulin heavy chain expression and reactivity of monoclonal antibodies RFA-1, -2, -3, -4 and OKT10 discriminate between majority B lymphocyte populations in the bone marrow and in peripheral lymphoid organs. In this study normal tissues and various B cell malignancies were studied in cell suspensions and tissue sections. Pre-B acute lymphoblastic leukaemia and multiple myeloma apparently reflect the phenotypes on normal B lineage cells of the bone marrow, while centroblastic-centrocytic lymphoma, B chronic lymphoid leukaemia (CLL) and prolymphocytic leukaemia (PLL) show the characteristics of distinct peripheral B lymphoid subsets found at different sites in the lymphoid tissue. These 'normal equivalent' cells are centroblasts and centrocytes in the germinal centre. CLL-like cells at the edge of the germinal centre (a minority population) and strongly Ig positive cells in the lymphocyte corona. Malignant cells in macroglobulinaemia are apparently more closely related to PLL and the corresponding normal peripheral B cells (in the corona) than to myeloma cells or the equivalent normal plasma cells in the bone marrow.

Antibodies, Monoclonal↗