G. Michlmayr

Redistribution of immunoglobulin determinants on human lymphocytes in lymphoproliferative disorders

Abstract Using 125I- or FITC-labelled anti-immunoglobulin antisera we studied the redistribution of surface Ig-anti-Ig complexes on the surface of human normal and neoplastic B lymphocytes, obtained from patients with chronic lymphocytic leukaemia and lymphosarkoma. The results were compared with those obtained from murine spleen cells. Whereas the majority of mouse lymphocytes exhibited cap formation under appropriate conditions, this staining pattern was only demonstrable on a very small, but distinct percentage of normal human lymphocytes and lymphosarcoma cells. In contrast typical cap formation was not observed on leukaemic blood lymphocytes. These findings are discussed with respect to the functional impairment of leukaemic lymphocytes.

Spontaneous and conA-induced suppressor lymphocytes: a comparative study.

Suppressor monocytes, Concanavalin A(ConA)-induced suppressor T cells, and short-lived suppressor lymphocytes have been describe in humans. The present study was performed to evaluate spontaneous suppression in a test system similar to that employed for the demonstration of ConA-induced suppressor cells: Lymphocytes were either stimulated by ConA (= induced suppressor cells) or immediately mitomycin-treated (= spontaneous suppressor cells). Both preparations were tested for their capacity to suppress mitogen-induced proliferation of autologous cells. Depletion of monocytes or B lymphocytes did not affect spontaneous suppression. The active cells were short-lived in vitro. Therefore the net increase in suppressor activity generated by preculture with ConA is in part related to a loss of spontaneous inhibitory activity in the control cultures kept without mitogen. Spontaneous suppressor cell activity was comparable to that of ConA-induced suppressor cells.

A Comparative Study of the Buoyant Density Distribution of Normal and Malignant Lymphocytes

SUMMARY Density distribution patterns of normal and malignant lymphocytes were compared following centrifugation to equilibrium on linear density gradients.

Surface immunoglobulins and receptor sites for aggregated IgG on leukemic reticuloendotheliosis cells

SummaryOn blood lymph nodes and spleen cells of 4 patients with leukemic reticuloendotheliosis (LR) the binding of125J-labelled IgG aggregates as well as binding of125J-labelled anti immunoglobulin sera was studied. Moreover the capacity to form spontaneous rosettes with sheep red blood cells to bind immune complement complexes as well as the proliferative response in the presence of PHA were investigated.On the surface of hairy cells a variety of immunoglobulins were demonstrable. IgG of both types was found to be the predominant surface bound immunoglobulin and evidence was obtained, that these antibodies were adsorbed from the serum via Fc-receptors. In all LR-cases the percentages of T-cell rosettes as well as the PHA responses were decreased when compared with the normal controls. The numbers of immune complement complex binding cells were in the range of the normal controls. Results are discussed with respect to the origin of hairy cells in LR.ZusammenfassungAn Blut-Lymphknoten und Milzzellen von 4 Patienten mit leukämischer Retikuloendotheliose (LR) wurde die Bindung125J-markierter IgG-Aggregate sowie von125J-markierten monospezifischen und polyvalenten Antiimmunglobulin-Serenuntersucht. Ferner wurde die Fähigkeit dieser Zellen zur spontanen Rosettenbildung mit Schaferythrozyten zur Bindung von Immun-Komplement-Komplexen sowie der proliferative Respons in Gegenwart von PHA getestet.An der Oberfläche von Haarzellen wurde eine Vielfalt von Immunglobulinen nachgewiesen. IgG beider Typen war das vorherrschende Immunglobulin, und Hinweise wurden erhalten, daß dieser Antikörper aus dem Serum durch Fc-Rezeptoren absorbiert wird. In allen Fällen von LR war der Prozentsatz von T-Zell-Rosetten ebenso wie der PHA-Respons gegenüber den Normalen vermindert. Der Anteil Immun-Komplement-Komplex bindender Lymphozyten war dagegen im Normbereich gelegen. Die Ergebnisse werden im Hinblick auf die Herkunft der Haarzellen bei LR besprochen.

Immunological characterization of lymphoproliferative disorders by membrane markers.

ZusammenfassungDie Charakterisierung verschiedener Lymphozytenpopulationen mittels Oberflächenmarker hat zum immunpathologischen Verständnis der verschiedenen lymphoproliferativen Erkrankungen wesentlich beigetragen. So konnte die chronische Lymphadenose als Erkrankung der B-Lymphozyten charakterisiert werden. Bei Patienten mit Morbus Hodgkin liegt der Anteil von B- und T-Lymphozyten im peripheren Blut annähernd im Normbereich. Die vermehrte Proliferation von T-Lymphozyten könnte auf einen gesteigerten Umsatz dieser Zellen im Rahmen einer Immunantwort hindeuten. Bei Patienten mit „Non-Hodgkin“-Lymphomen konnte ein vermehrter Anteil von B-Lymphozyten in befallenen Lymphknoten gefunden werden, im peripheren Blut war diese Vermehrung allerdings selten. Veränderungen der einzelnen Lymphozytenpopulationen bei den verschiedenen Formen von „Non-Hodgkin“-Lymphomen sowie die seltenen Formen von T-Zell Lymphomen (lymphoblastolische Lymphome und Sézary-Syndrom) werden besprochen. Die Ergebnisse bei Immunozytomen und Myelomen werden im Hinblick auf die verschiedenen Reifungsstufen der B-Lymphozyten diskutiert.SummaryThe characterization of lymphocyte subpopulations by means of surface markers improved our understanding of the immunopathology of lymphoproliferative disorders. In chronic lymphocytic leukemia an accumulation of B-lymphocytes have been documented. The antibody deficiency syndrome in these patients might well reflect a maturation defect of the leukemic B-lymphocytes. In patients with Hodgkins disease the relative number of B- and T-lymphocytes in the blood was not markedly altered in comparison to normal controls. An increased proliferation primarily of T-lymphocytes however, might suggest their accelerated turnover as an indication of the host response. In most patients with “Non-Hodgkin” lymphomas high numbers of B-lymphocytes were found in affected lymph nodes, and these appear occasionally in the peripheral blood. Differences in immunopathological manifestations of the various subgroups of the “Non-Hodgkin” lymphomas are emphasized and the rare occurrence of lymphomas of T-lymphocytes (mainly observed in lymphoblastic lymphomas and in Sézary syndrome) is discussed. Immunopathological alterations in immunocytomas and the myelomas are considered in respect to the involvement of B-lymphocytes at different stages of maturation.

Normal Suppressor-Cell Activity in Systemic Lupus Erythematosus. ASstudy on 26 Cases

Suppressor-cell activity of 26 SLE patients suffering from active disease was compared to that of 15 healthy controls. ConA-induced and spontaneous suppression was evaluated. The mitogen-driven proliferation of normal allogeneic cells was significantly impaired by ConA-induced as well as spontaneous suppressor cells. However, no difference in suppressor-cell activity could be demonstrated between SLE patients and controls.

Die Differenzierung menschlicher Blutlymphozyten mit immunologischen Methoden

In 47 patients with acute lymphoblastic leukemia surface markers were evaluated on mononuclear cells of the peripheral blood as well as in some cases on bone marrow lymphocytes. The lymphocytes were characterized by their binding capacity for sheep red blood cells, the demonstration of Fc-receptors, complement receptors as well as surface immunoglobulins. In 6 of 23 untreated patients the blasts bound sheep red blood cells spontaneously (T-ALL), in two of these six cases the lymphoblasts had simultaneously receptors for complement. In a further patients the lymphoblasts had complement- and Fc-receptors. The blasts of 16 of 23 patients were negative in respect to the markers tested (O-ALL). By comparing two groups of patients--one with positive cells, one unreactive--the clinical features differed: the marker positive group showed a predominance of male patients, 5 of 7 patients had a massive mediastinal mass and the remission rate was lower than in the group with positive blasts. 24 patients in remission under maintance treatment had a decreased percentage of rosette forming lymphocytes as well as lymphocytes with surface immunoglobulins and Fc-receptors. There existed some correlation between the percentage of rosette forming lymphocytes and the clinical course: patients with complications had lower percentages of rosette forming lymphocytes than patients with a favourable course.

Die Differenzierung menschlicher Blutlymphocyten mit immunologischen und autoradiographischen Methoden@@@The differentiation of human blood lymphocytes by means of immunologic and autoradiographic methods: I. Ergebnisse bei Normalpersonen und bei Patienten mit chronischer Lymphadenose

SummaryCirculating lymphocytes consist of a heterogenous cell population. Employing immunological and autoradiographic methods lymphocytes with Ig (kappa) determinants, those with membrane receptors for immune-complement complexes, lymphocytes containing Ig intracellularly and those in DNA synthesis were evaluated in normals and in patients with chronic lymphocytic leukaemia (CLL). The concept of functionally defective lymphocytes in CLL was further substantiated. The use of immunological markers for identifying thymus (T)- and bone marrow (B) derived human lymphocytes is discussed.ZusammenfassungZirkulierende Lymphocyten setzen sich aus funktionell heterogenen Zellen zusammen, welche mit morphologischen Methoden allein nur ungenügend differenziert werden können. Unter Verwendung immunologischer und autoradiographischer Methoden wurden Lymphocyten mit Determinanten leichter (kappa) Ketten, Lymphocyten mit Membranreceptoren für Immun-Komplement-Komplexe, lymphatische Zellen mit cytoplasmatischem Immunglobulingehalt und Lymphocyten in DNS-Synthese bestimmt.Gegenüber Normalpersonen waren bei Patienten mit chronischer Lymphadenose Abweichungen an mehreren dieser Lymphocytenpopulationen nachweisbar. Die Ergebnisse werden im Hinblick auf das Konzept thymus- und knochenmarkabhängiger Lymphocyten diskutiert, deren Differenzierung mit immunologischen Methoden erleichtert wird.

Surface glycoproteins (S-GP) on normal and malignant human leukocytes.

SummaryThis study aimed to investigate high molecular weight surface glycoprotein (S-GP) patterns on various types of human leukocytes. S-GP were externally labelled by the Galactose-oxidase-NaB3H4 technique. Results based on the analysis of 120 samples derived from different types of normal and malignant leukocytes indicate that (i) the relative expression of high molecular weight S-GPs changes during haemopoietic cell differentiation and (ii) to some extent these changes enable the classification of human leukocytes.

Insoluble PHA – A B-Cell Mitogen in Man?

Blood lymphocytes of normal individuals and of patients with chronic lymphocytic leukemia were evaluated for their blastogenic response to insoluble PHA. In at least preferential stimulation of normal B-lymphocytes was observed, whereas leukemic lymphocytes were almost insensitive. This result supports the hypothesis of a functionally defective B-lymphocyte population in chronic lymphocytic leukemia.