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Renal biopsy and autopsy specimens were studied in 43 patients with renal complications of multiple myeloma and correlated with immunoelectrophoresis (IEP) and other clinical data at the time of biopsy. Lesions specifically related to multiple myeloma fell into two categories, with different patterns of protein excretion. (1) Myeloma Cast Formation: When other lesions which might contribute to renal insufficiency (RI) were excluded, there was a good correlation between the extent of myeloma cast formation and severity of RI. Sixteen of 19 patients excreted free light chains (LCs) in the urine, in seven as the predominant or sole urinary protein. (2) Tissue Deposition of Paraproteins: Nine cases had generalized glomerular, tubular basement membrane and vascular deposits of presumed kappa-chains (one with associated alpha-heavy chains). Four patients, all with myelomas secreting lambda LCs, had diffuse amyloid deposits in similar distribution. All patients (save two who were anuric) had diffuse, nonselective proteinuria by IEP, most within the nephrotic range. Four patients had free LCs in the urine, but in none was this the predominant component. Cast nephropathy and LC tissue deposition tended to occur in mutually exclusive fashion. Cases with diffuse tissue deposits of LCs showed few or no myeloma casts. Cases with cast nephropathy had only occasional mild mesangial lesions and focal interstitial and vascular deposits of amyloid. Evidence indicates that these lesions represent incidental LC deposition in cases whose basic lesion is longstanding and/or severe cast nephropathy, and that their contribution to RI is minor in comparison to that of the myeloma casts.

The simultaneous detection of multiple myeloma and acute myeloblastic leukaemia is reported in two patients who had not undergone chemotherapy. Histological examinations confirmed the infiltration by both myeloblasts and plasma cells. Only the latter contained monoclonal immunoglobulin chains at immunofluorescent studies. The possible relation between the two distinct proliferative processes is briefly discussed.

An IgG antibody found in the serum of a thrombasthenic patient reacted in complement fixation with platelets from 350 normal individuals but was nonreactive with platelets from eight other thrombasthenic patients. ADP-induced aggregation of normal platelets was inhibited by the patient's antibody. Family studies using the quantitative complement fixation test showed that healthy heterozygotes were easily distinguishable from normal or thrombasthenic individuals since their platelets had an intermediate amount of the reactive antigen. Indirect immunoprecipitation tests using this serum and soluble membrane antigens labeled with iodine-125 that had been extracted from normal platelets by the detergent Nonidet P-40 gave a single radioactive peak at 120,000 mol wt in sodium dodecyl sulfate polyacrylamide gel electrophoresis. A similar estimate of the molecular weight was obtained from Sephadex G-200 filtration of the soluble antigens extracted from normal platelets by spontaneous release or chaotropic agents and tested in complement fixation with the patient's serum. These findings strongly suggest that the molecule recognized by this antibody is absent or structurally modified in thrombasthenia cases and that it may be involved in platelet aggregation.

We report here the study of early events following surface Ig cross-linking such as Ca2+ mobilization and IP3 generation, in chronic lymphocytic leukemia (CLL) B cells. Those leukemic populations were previously shown to be frozen at different stages of activation with unique requirements for proliferation. The study reported here disclosed 3 patterns of response in terms of Ca2+ mobilization and proliferation. These results are interpreted in terms of differential anti-mu signalling on B cells at different stages of activation.

We compared the proliferative responses of purified human leukemic B cells from 12 cases of chronic lymphocytic leukemia to highly purified B cell growth factor (BCGF) and recombinant interleukin 2 (rIL 2) spontaneously, and in a coactivation assay using anti-mu monoclonal antibodies. Heterogeneity of response to one or the other lymphokine was observed from case to case. Spontaneous responses were observed to BCGF in one case, to rIL 2 in 3 cases and to both lymphokines in one other case. Costimulation with anti-mu monoclonal antibody induced a proliferative response to BCGF in 3 additional cases and to rIL 2 in 4 cases. Interestingly, cells from BCGF-responsive cases also proliferated in response to rIL 2. The leukemic B cells from 4 chronic lymphocytic leukemia patients were unresponsive. Cells from 5 cases expressed IL 2 receptors, although rIL 2 induced a direct proliferative response in only 3 of these cases. Expression of the B cell activation antigen B5 was associated to BCGF responsiveness.

The incidence of malignancies is strikingly high in patients with primary immunodeficiency diseases. Analysis of clinical data and the types of neoplastic proliferations raise several hypothesis. Occurrence of cancers does not seem to be favored by secondary immunodeficiencies related to lymphoma or immunosuppressive therapy.

In two patients with Waldenström's macroglobulinaemia complicated with peripheral neuropathy, purified monoclonal immunoglobulin M showed antibody activity specifically directed against vimentin, a major polypeptide of mesenchymal cell cytoskeleton and therefore in Schwann's cell. The neuropathy was of the sensory-motor type. It was improved in one case by plasma exchanges combined with chemotherapy. The relevance of this original antibody activity to the pathogenesis of neuropathy is discussed.

Homozygous C2 deficiency in a 19-year-old boy was associated with variable immunodeficiency manifested by marked hypoimmunoglobulinemia and impaired antibody responses, normal circulating B lymphocytes, and subnormal T-cell functions. Neither antilymphocytic autoantibodies nor chromosomal abnormalities were found. Serum immunoglobulin levels were within normal limits in his parents and brother who were heterozygous for C2 deficiency. The patient's lymphocytes were homozygous at the HLA-D locus but expressed an antigen different from DW2.

The distribution of DQ as well as DR antigens was examined on lymphoid and monocytic cells at different stages of differentiation. In the B cell series, both immature and differentiating (under Staphylococcus aureus or pokeweed mitogen stimulation) B cells often lacked DQ molecules; among surface IgM+ and IgD+ cells, both DQ and DR molecules were detected except on cells from 30% of the lymphoid malignancies studied. T cells expressed DQ molecules only after stimulation; a DQ-DR+ phenotype was observed in a large number of cells after allogeneic stimulation, in certain antigen-specific T cell lines as well as in T cell lymphomas, suggesting that class II antigens had a distinct pattern of regulation. In the monocytic lineage, DQ molecules were expressed by most lymph node monocytes and only a low percentage (20%) of circulating monocytes.

Monoclonal IgM from patients with peripheral neuropathies frequently have an antibody activity directed against myelin-associated glycoprotein (MAG). Reactivity of 19 of these sera with avian embryonic tissues was compared. Immunohistological studies allowed their classification into distinct groups according to the staining pattern. Both neural and non-neural cell lineages were recognized by these antibodies. The IgM specificities were also compared with those of the monoclonal antibodies HNK-1 and NC-1, which react with MAG and some cell adhesion molecules. Only one group displayed a pattern of staining similar to that observed with these monoclonals. The reactivity of these IgM paraproteins with two cell adhesion molecules, neural cell adhesion molecule and neuron-glia-cell adhesion molecule by immunoblotting confirmed the heterogeneity found in the histological study.

Human alpha heavy chain disease (HCD) is characterized by the presence in patient's serum of a short Ig alpha chain devoid of light chains. We analyzed the serum protein, the alpha HCD mRNA and the productive rearranged H chain gene from the leukemic cells of a new case (YAO) of alpha HCD. The abnormal YAO alpha 1 Ig was devoid of VH and CH1 domains and started at the beginning of the hinge region. The alpha HCD mRNA was shorter than normal alpha mRNA and the cDNA prepared from YAO mRNA encoded a leader sequence, an insert of 70 nucleotides and the CH2 and CH3 exons. The origin of the inserted sequence was assessed by cloning and sequence analysis of the alpha 1 productive gene. It started with a leader exon, a leader-VH intron and the first 11 bp of a VH exon. Then the VH region was deleted and replaced by a 19-nucleotide sequence that turned out to correspond to the 3' part of a modified JH5 exon. It was followed by a 221-bp sequence homologous to the JH5-psi JH3 intron and by an inserted sequence of unknown origin. The 3' part of this insertion and the remnant of a JH6 exon delineated a third exon that was followed by a relatively conserved JH6-C alpha intron. These two composite exons were flanked by splicing sites and accounted for the 70-nucleotide insert of the cDNA. The genomic nucleotide sequence also revealed a large deletion in the switch CH1 region which eliminated normal splicing sites and resulted in splicing of the third exon directly to the CH2 exon.

The histogenesis of Ewing sarcoma is still controversial; we therefore studied the expression of intermediate filaments (IF) in cell lines derived from Ewing tumors since identification of IF in tumor cells is considered a reliable marker of tissue origin and differentiation. All nine lines studied expressed vimentin IF; in addition, a small number of Ewing cells from three lines expressed keratin filaments. After treatment with phorbol esters, a high percentage of cells from these three lines synthesize keratin IF identified by immunoblotting as keratin 8 and 18 polypeptides, which are expressed by single epithelia and epithelial cells in early embryonic development. Furthermore cells from a fourth line synthesize keratins after transplantation in nude mice. These data indicate that, under certain conditions, undifferentiated Ewing cells may acquire an IF phenotype related to that of epithelial cells.

In 11 patients, sera displaying a ringlike nuclear immunofluorescent staining on sections of rat liver tissue were shown by Western blotting to contain antibodies to lamins. Sera from 8 patients contained autoantibodies reacting with lamin B, whereas sera from the other 3 patients reacted with lamins A and C. All patients (9 women and 2 men) had a chronic autoimmune disorder, which rarely fulfilled the usual criteria for a diagnosis of systemic lupus erythematosus. The disorder was characterized by acute or chronic (active or granulomatous) hepatitis; steroid-responsive blood cytopenia, often associated with a circulating anticoagulant, or anticardiolipin antibodies, or both; and cutaneous leukocytoclastic angiitis or probable brain vasculitis. Eight patients had at least two of these three conditions. Antilamin autoantibodies may thus be a marker for an unusual subset of autoimmune diseases.

alpha-H chain diseases (HCD) is a human lymphoproliferative disorder, characterized by the production of truncated alpha-Ig H chains, without associated L chains. In this study, we have analysed the serum protein, the alpha-HCD mRNA and the rearranged alpha-HCD gene from the leukemic cells of a patient (MAL) with alpha-HCD. The abnormal MAL serum Ig consisted of short alpha 1-chains, lacking VH and CH1 domains (only CH2 and CH3 domains were present). The alpha-HCD mRNA (1.2 kb) was shorter than a normal alpha-mRNA (2 kb); the corresponding cDNA had sequences for the leader, a 84-bp sequence of unknown origin and the CH2 and CH3 exons. The establishment of the sequence of the productive alpha-HCD MAL allele revealed two major deletions; that of the VH region as well as that of the CH1 region. The JH region is altered by multiple mutations, small insertions and a duplication of the psi JH3 region. A large insert (INS1), of 360 bp (containing the 84 bp exon found in the cDNA), replaces the deleted VH region. INS1 is non-Ig related and apparently of nongenomic origin. A large second insert (509 bp), is located between the enhancer and the switch region. Insert2 contains repetitive non-Ig-related sequences and a small Ig-related sequence. All these alterations resulted in an abnormal mRNA, which comprises the leader, a 84-bp alien exon derived from INS1 and the CH2 and CH3 exons of the alpha 1-gene.

The authors report the chance discovery in a man aged 53 years with serum positive rheumatoid arthritis, of gamma 3 heavy chain disease. The originality of this case depended on the absence of any detectable lymphoid proliferation and on the transient character of the pathological protein. Only the course after a long follow up will determine whether there is no incipient lymphoid proliferation and whether the heavy chain disease has disappeared permanently.

Proliferating cells from twenty-four patients with alpha- or gamma-heavy chain disease (HCD) were studied by direct immunofluorescence and in several cases by biosynthesis experiments with 14C-amino acid incorporation. In twenty-two patients, the cells contained the HCD proteins only and no light chain synthesis could be detected. Conversely, apparently non-secreted monotypic light chains were found in one case of gamma-HCD and one case of alpha-HCD. The proportion of proliferating cells containing cytoplasmic heavy chains, their appearance and the presence or not of surface heavy chains showed great variation from patient to patient. In some cases, the proliferation predominantly affected either plasma cells or lymphocytes whereas in others the disease seemed to correspond to a proliferation of HCD protein-bearing lymphocytes with persistent maturation into plasma cells. Large cell lymphomas supervening on alpha-HCD belonged to the same proliferating clone as the clone secreting the HCD protein, as shown by surface markers and biosynthesis experiments which demonstrated synthesis but no secretion of HCD proteins. In one patient with gamma-HCD, the cells carried surface gamma and delta chains.

The clinical, hematologic and pathologic findings in seven patients were similar to those of Waldenström's macroglobulinemia, but unexpectedly the serum monoclonal immunoglobulin belonged to the IgG class in five patients and to the IgA class in two. The bone marrow and lymph node lymphoid proliferation was pleomorphic, with the simultaneous presence of small lymphocytes, normal mature plasma cells and transitional lymphoplasmacytic cells. Immunofluorescence studies showed that a monoclonal immunoglobulin similar to that found in the serum was detectable on the membrane or in the cytoplasm of all the proliferating cells, which thus belonged to the same B cell clone. The study of these patients is in accordance with the concept that lymphoid disorders featured by a pleomorphic monoclonal B cell proliferation constitute a distinct clinicopathologic entity, which is not restricted to IgM-producing clones.

The expression of vimentin, the major polypeptide of the intermediate filament (IFM) cytoskeleton of lymphoid cells, was studied in normal and malignant human lymphoid cell lines. Cells from 24 of 27 Burkitt's lymphoma cell lines (BLCL) were found to have an absent (16 lines) or decreased (8 lines) expression of vimentin IFM. In contrast, non-Burkitt's malignant lymphoid cell lines (5 lines) and lymphoblastoid cell lines (LCL) derived from normal B-cells (45 lines) exhibited a well-developed vimentin IFM network. However, low expression of vimentin was also found in 3 LCL derived from patients with the Langer-Giedion syndrome, which is characterized by a deletion of the distal end of chromosome 8. Treatment of vimentin-negative BLCL and Langer-Giedion LCL with azacytidine led to a transient reexpression of vimentin.

Recombinant interleukin (IL) 4 has been shown to be able to up-regulate low-affinity Fc receptor for IgE (Fc epsilon RII)-CD23 expression on B cells as well as on other human mononuclear cells. We demonstrate here that, in opposition with previous reports, recombinant IL2 also can up-regulate CD23 expression on B cells. This was first observed on CLL cells which represent a monoclonal proliferation of B cells arrested at an intermediate stage of activation. Cells of 5 out of 12 B-CLL studied display such an increase and all 5 proliferated, in vitro, directly in response to IL2. Similarly, upon triggering with anti-mu and IL2, normal tonsillar B lymphocytes also demonstrate an increase of CD23 expression but this was observed only on day 3. Interferon-gamma was able to inhibit this IL2-mediated up-regulation of CD23 on normal B cells but not on CLL-B cells; on those cells interferon-gamma was similarly unable to inhibit the IL4-mediated CD23 up-regulation. These results suggest that CD23 regulation is complex and related to the stage of activation and the cell type.

We demonstrate here that purified recombinant interleukin 2 (IL-2) induces a sizeable population of highly purified spleen B cells, by both negative and positive (cell-sorting) selection to differentiate polyclonally into plasma cells. This effect is seen at concentrations of IL-2 that are optimal for T-cell growth (1-5 U/ml) and is inhibitable by anti-Tac monoclonal antibody. In contrast, peripheral blood B cells show no or minimal terminal differentiation. When spleen B cells were separated into small and large cells, only the latter responded to IL-2; since this state of activation is achieved in vivo, these data support the possibility that IL-2 may be a physiological mediator in B-cell differentiation.

Monoclonal IgM from patients with peripheral neuropathy frequently have anti-myelin-associated glycoprotein (MAG) activity. We investigated the idiotypes of 10 monoclonal anti-MAG by using rabbit polyclonal antisera. Three groups of anti-idiotypic antisera could be distinguished. Four sera reacted only with the immunizing protein. Two sera reacted with a single other anti-MAG IgM in addition to the immunizing one. Immunoenzymatic studies showed that these two couples of anti-MAG IgM reacted identically with 100% cross-inhibition, indicating that the whole set of idiotypes identified by the rabbit antiserum was present on both IgM antibodies. The four other anti-idiotypic sera reacted with the homologous IgM, as well as with most of the other anti-MAG IgM. In contrast to the previous antisera the binding of these four sera to the homologous IgM could not be inhibited by other cross-reacting anti-MAG IgM. However, when a heterologous IgM was used for coating, these antisera with one exception showed complete cross-inhibition. The absence of inhibition by purified MAG of the patient of the anti-idiotypic antisera sera suggests that these antibodies are most likely to be directed against framework determinants rather than against combining site epitopes.

We have studied the alterations of vimentin intermediate filaments in uninduced or differentiated HL60 and U937 human leukemic cell lines. Whereas uninduced lines exhibited only a discrete reseau of vimentin, TPA treated cells acquire a very rich vimentin network similar to that of normal monocytes. On the other hand, DMSO treated HL60 cells differentiate to polymorphonuclears without modification of the IF network. These findings indicate that leukemic cells retain the expression of vimentin and exhibit an IF network similar to that of their normal counterpart.

In a 66-year old man without previous major disease the unexpected finding of pancytopenia on routine blood count during an acute respiratory infection led to the diagnosis of IgG-producing myeloma without radiological bone lesions, associated with partial blastocytosis and abnormalities in granulocyte maturation. No treatment was given. Within 15 days, the circulating blastocytes became more numerous and type M1 acute myeloblastic leukaemia was diagnosed. A combined rubidazone and cytosine arabinoside treatment failed, and the patient died rapidly.

The mode of action and the target cell of a suppressive factor continuously and spontaneously produced by a human hybrid T cell line constructed recently are reported. This factor was shown to suppress pokeweed mitogen-induced B cell differentiation when added within the first 48 hr of culture. It does not suppress B cell differentiation induced by Nocardia extracts, a relatively T-independent mitogen. The target cell for this factor seems to be a T lymphocyte in that it can be absorbed by E-rosetting cells but not by B lymphocytes or monocytes. This factor does not impair mitogen or allogeneic-induced lymphocyte proliferation and has an apparent m.w. of approximately 45,000 as estimated by Sephacryl S200 gel chromatography.

Intermediate filaments (IF) constitute a major cytoplasmic filamentous network of higher eukaryotic cells that is distinct from actin and myosin microfilaments or microtubules. Although structurally similar, these filaments are formed by chemically and antigenically different proteins. Vimentin is the major IF polypeptide of mesenchymal cells and cultured non-mesenchymal cell lines. Recently, we have characterized a monoclonal IgM antibody from a patient with Waldenström's macroglobulinaemia which is directed against vimentin. Using this monoclonal antibody, we have shown by direct immunofluorescence that intermediate filaments of human B and T lymphocytes consist of vimentin. In cells exposed to colcemid, the intermediate filaments retracted into a juxtanuclear aggregate ('coli') characteristic of vimentin filaments. As most components of the cytoskeleton, especially actin and myosin, have been implicated in the capping phenomenon, we investigated the effect of capping of either beta 2-microglobulin or membrane immunoglobulins on the organization of the intermediate filament network. We report that capping of these surface molecules induced the redistribution of vimentin just beneath the cap. When colcemid-treated cells were allowed to cap, the location of the cap always coincided with the coil, suggesting that the anchorage point of intermediate filaments is situated within the uropod.

Neoplastic cells from 9 patients affected with a "histiocytic" lymphoma were studied with 5 membrane markers of B or T lymphocytes. In 2 patients a monoclonal B-cell proliferation was found; they had been affected previously with well documented B-cell proliferations: chronic lymphocytic leukemia or Waldenström's macroglobulinemia. The blast cells of 2 other patients had T-cell features; in a fifth case, the abnormal cells carried only a strong receptor for the Fc fragment of IgG, which suggested their truly monocytic origin. In 4 patients, the cells had no detectable surface markers. These findings demonstrated that this group of lymphomas is heterogenous, that the term "histiocytic" appears to be wrong in most instances, and that the cellular origin of the malignant cells frequently remains unidentified and thus prevents a satisfactory new classification.

Adult and one week old marmosets were injected intravenously within a one month period or intraperitoneally within a 6 week period respectively, with monoclonal IgM having an anti-myelin associated glycoprotein antibody activity. No clinical or electrophysiological abnormalities could be detected in experimental animals. However, indirect immunofluorescence studies showed IgM deposition in close contact to myelin sheaths. Minor but distinct alterations of nerves were found in the adult: the enlargement of Schmidt-Lanterman incisures seen in electron microscopy could explain the decrease of the proportion of fibers of small diameter found by morphometry of semi-thin section, and the reduction of the mean internodal length in fibers of a given diameter seen in teased nerve fibers studies.

Several rabbit antisera to T cells obtained from various sources (thymus, peripheral blood, brain, T-derived leukemias) were studied with the aim to obtain reagents specific for a subset of T cells. Sera were first absorbed on human tissues and B cells; thereafter these T cell-specific sera were additionally absorbed with T cells of different origin and especially with leukemic T cells, which are likely to represent a clonal expnasion of a subset of T cells with potentially unique antigenic markers. Three antigenically distinct subpopulations of T cells were delineated. The relationship of these subsets with previously defined human T cell subpopulations (T subsets with a receptor for the Fc or IgG or IgM or with a receptor for a lectin from wheat germ agglutinin) was investigated.

The proliferative responses of purified leukemic human B cells from nine B cell chronic lymphocytic leukemias to recombinant interleukin 2 (IL-2), spontaneously, and after preactivation by Staphylococcus aureus Cowan I (SAC) or anti-mu antibodies were studied. Three patterns of response were observed: (a) no response (three cases); (b) a moderate spontaneous response enhanced by anti-mu (one case); (c) a high proliferative response after preactivation by anti-mu and/or SAC (five cases). IL-2 could also trigger normal B cells, purified from spleen, to proliferative after preactivation by anti-mu or SAC. These results provide evidence that IL-2 is a lymphokine that acts physiologically on both B and T cells.

Case records of 14 women with spontaneous recurrent fetal wastage were analyzed. Venous and/or arterial thrombosis developed in nine patients and vasospastic symptoms in eight. Every patient had some kind of autoantibodies: prothrombin activation inhibitor was present in seven cases, anticardiolipin in five, and, antimitochondrial antibodies in two. Antinuclear antibodies were present in seven cases, and significant titer of antibodies to single-stranded DNA in nine cases. With a mean follow up of 6.5 years no patient developed systemic lupus erythematosus. It is suggested that such women have a peculiar form of vasculitis.

The chromosomes of an Epstein-Barr virus-negative European Burkitt's lymphoma cell line were studied. All the cells carried the t(8;14) translocation. One clone had 51 chromosomes and was (+1,+7,+16,+15,+21), whereas another clone also had 51 chromosomes but was (+1q+,+7,+16,+15,+21). A third clone had 46 chromosomes (4q+/-).

Bone marrow cells from 14 patients with primary amyloidosis and two patients with myeloma amyloidosis were studied by immunofluorescence and biosynthesis experiments after incorporation of radioactive amino acids. Cells from four patients affected with non-myeloma secondary amyloidosis were also studied as controls. In primary amyloidosis, monoclonal plasma cell populations were demonstrated by immunofluorescence in virtually every case, even in patients without serum and urine monoclonal immunoglobulin and with a normal percentage of bone marrow plasma cells. Biosynthesis experiments showed the secretion of large amounts of free light chains, most often of the lambda type, in every primary or myeloma amyloidosis case and the presence of light chain fragments in almost all cases. Special features in certain patients were the synthesis of short gamma chains (two cases), assembly block at the HL half molecule level of a monoclonal IgA (one case) and secretion of decameric abnormally large kappa chains (one case). This is in contrast with non-myelomatous secondary amyloidosis where the distribution of bone marrow plasma cells was normal by immunofluorescence and where normal sized immunoglobulins were synthesized, without free light chain secretion and fragments. These data confirm that primary amyloidosis belongs to plasma cell dyscrasias and emphasize the role of free light chains and light chain fragments in the pathogenesis of amyloid deposition.

Monoclonal membrane-bound Ig were found by immunofluorescence on the lymphocytes in the vast majority of cases of chronic lymphocytic leukemia. The distribution of H and L chains among these patients reflected the distribution of surface Ig on normal lymphocytes and IgM was the predominant class. The importance of the study of surface Ig synthesized in vitro is outlined. The simple staining of freshly drawn cells may lead to erroneous conclusions, since an apparently polyclonal staining can result from the anti-IgG antibody activity of a monoclonal surface IgM, from the attachment of immune complexes at the lymphocyte surface or from the binding of serum antibodies to cell membrane determinants. A biclonal proliferation, characterized by distinct surface-Ig markers, was demonstrated in several cases of chronic lymphatic leukemia. Monoclonal surface Ig were also detected on the lymphoblasts in 2 cases of acute transformation of chronic lymphocytic leukemia, in several patients with acute lymphosarcoma cell leukemia and in 1 case of acute lymphatic leukemia. In most cases of acute lymphatic leukemia, the leukemic cells were devoid of detectable B- or T-cell membrane markers. In 2 cases of acute lymphatic leukemia, 1 case of chronic lymphatic leukemia and in all patients with the Sezary syndrome, the leukemic cells appeared to be thymus-derived.

Lymphoma cells from 25 patients were studied for the presence of B lymphocytes (membrane bound Ig and Fc receptor) and T lymphocytes (rosette formation with sheep erythrocytes) membrane markers. All cases of well differentiated lymphocytic lymphoma and of acute lymphosarcoma cell leukaemia and most cases of poorly differentiated lymphocytic lymphoma behaved as B cell monoclonal malignancies. However, the malignant cells of some patients were not definitely classified according to their B or T cell origin or lacked these membrane markers. The latter situation was encountered in 4 reticulum cell sarcomata. Polyclonal Ig were found on the surface of B cells in a case of hyperbasophilic undifferentiated lymphoma. The need for using several membrane markers to study the abnormal lymphoma cells is outlined. Such studies improve our understanding of these malignancies and may lead in the future to a satisfactory classification of non-Hodgkin lymphomata.

Although recently identified, this disease is by no means exceptional. It is characterized by the deposition in various organs of an amorphous substance which differs from the amyloid substance and contains monoclonal immunoglobulin determinants: either a light kappa or lambda chain, or a light and a heavy chain. The severity of the disease is due to various organs being involved, notably the kidneys. There is in every case a monoclonal plasmocytic or lymphoplasmocytic proliferation which may appear as benign. In almost one-third of the cases no monoclonal immunoglobulin can be detected in the serum. In a study of immunoglobulin biosynthesis, 6 out of 8 patients showed striking structural abnormalities. The relationship between these very unusual lg's and tissue deposition is discussed in detail.