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Objective: Hereditary haemorrhagic telangiectasia (HHT) is a genetic disorder related to mutations in one of the coreceptors to the transforming growth factor-β superfamily (ALK1 or endoglin). Besides the obvious vascular symptoms (epistaxis and arteriovenous malformations), patients have an unexplained high risk of severe bacterial infections. The aim of the study was to assess the main immunological functions of patients with HHT using the standard biological tests for primary immunodeficiencies., Design, Setting and Subjects: A prospective single-centre study of 42 consecutive adult patients with an established diagnosis of HHT was conducted at the National French HHT Reference Center (Lyon). Lymphocyte subpopulations and proliferation capacity, immunoglobulin levels and neutrophil and monocyte phagocytosis, oxidative burst and chemotaxis were assessed., Results: Innate immunity was not altered in patients with HHT. With regard to adaptive immunity, significant changes were seen in immunological parameters: primarily, a lymphopenia in patients with HHT compared with healthy control subjects affecting mean CD4 (642 cells μL(-1) vs. 832 cells μL(-1) , P < 0.001), CD8 (295 cells μL(-1) vs. 501 cells μL(-1) , P < 0.0001) and natural killer (NK) cells (169 cells μL(-1) vs. 221 cells μL(-1) , P < 0.01), associated with increased levels of immunoglobulins G and A. This lymphopenia mainly concerned naïve T cells. Proliferation capacities of lymphocytes were normal. Lymphopenic patients had a higher frequency of iron supplementation but no increase in infection rate. Lower levels of immunoglobulin M and a higher rate of pulmonary arteriovenous malformations were found amongst patients with a history of severe infection., Conclusions: Patients with HHT exhibit immunological abnormalities including T CD4, T CD8 and NK cell lymphopenia and increased levels of immunoglobulins G and A. The observed low level of immunoglobulin M requires further investigation to determine whether it is a specific risk factor for infection in HHT., (© 2013 The Association for the Publication of the Journal of Internal Medicine.)

Sjögren's syndrome (SS) is an autoimmune disease targeting the exocrine glands resulting in xerostomia/keratoconjunctivitis sicca. Presently, we examined the levels and clinical correlations of IL-22 in SS. Patients with SS together with normal controls were randomly selected. IL-22 was detected at significantly higher levels in sera of patients with SS. The levels of IL-22 present in sera showed statistically significant direct correlations with hyposalivation, anti-SSB, anti-SSA/SSB combined, hypergammaglobulinemia and rheumatoid factor. IL-22 showed a direct correlation with major clinical parameters. The data suggest that IL-22 plays a critical role in the development of SS, and further study is needed to examine its function in human SS., (© 2011 The Authors. Scandinavian Journal of Immunology © 2011 Blackwell Publishing Ltd.)

BAFF-R is the predominant receptor that mediates B-cell activating factor (BAFF)-dependent B-cell signalling and plays a critical role in late-stage B-cell maturation and survival. BAFF has been implicated in the development of autoimmunity and systemic lupus erythematosus (SLE). To define the role of BAFF-R in autoimmunity and SLE, we crossed A/WySnJ mice with MRL-lpr mice and generated BAFF-R-mutant MRL-lpr mice. The BAFF-R mutation markedly impaired the development of immature, mature and marginal zone B cells in the spleens of MRL-lpr mice. Unexpectedly, the BAFF-R mutation in MRL-lpr mice did not result in decreased autoantibody production, hypergammaglobulinaemia or immune complex-mediated glomerulonephritis. Rather, the ability of BAFF-R-mutant lpr splenic B cells to produce immunoglobulins in vitro was not decreased, although germinal centre formation, antibody response and B-cell proliferation were impaired. Further studies found increased numbers of B cells in the bone marrow of BAFF-R-mutant MRL-lpr mice compared to the BAFF-R-intact lupus mice. ELISPOT analysis revealed that BAFF-R-mutant MRL-lpr mice had more antibody-secreting cells in their bone marrow than the control mice. Thus, these findings could explain the development of autoimmunity and hypergammaglobulinaemia observed in BAFF-R-mutant MRL-lpr mice.

Background: Classical type hyper-immunoglobulin D (IgD) syndrome (HIDS) is an hereditary auto-inflammatory disorder, characterized by recurrent episodes of fever, lymphadenopathy, abdominal distress and a high serum concentration of IgD. It is caused by mevalonate kinase deficiency., Objective: To further characterize the acute phase response during fever attacks in HIDS in order to improve diagnosis., Subjects: Twenty-two mevalonate kinase-deficient HIDS patients., Methods: Blood samples were drawn during and in between febrile attacks, and concentrations ofC-reactive protein (CRP), ferritin, procalcitonin, pentraxin 3, IgD and cholesterol in several lipoprotein fractions were determined., Results: The marked acute phase response at the time of a fever attack in classical type HIDS is reflected by a rise in CRP accompanied by a moderate but statistically significant rise in procalcitonin and pentraxin 3. In only two of 22 patients, procalcitonin concentration rose above 2 ng mL(-1) during fever attack, compatible with the noninfectious nature of these attacks. Ferritin does not reach the high concentrations found in adult-onset Still's disease. Despite the defect in mevalonate kinase, a component of cholesterol metabolism, serum cholesterol did not change during attacks. IgD concentration is elevated regardless of disease activity, although there is appreciable variation during life. Its role in HIDS remains unclear., Conclusion: The combination of high CRP concentration plus procalcitonin concentration <2 ng mL(-1) in a symptomatic HIDS patient might indicate a febrile attack without (bacterial) infection; this observation warrants further investigation for its usefulness as a marker in clinical practice.

A healthy 60-year-old patient presented with progressive dyspnoea. Clinical, radiographic and pathological features of interstitial lung disease were found and an open lung biopsy established the diagnosis of usual interstitial pneumonitis (UIP) (idiopathic pulmonary fibrosis). Despite treatment, the patient died 4 months later in respiratory failure. Although the patient had no extra-thoracic involvement at autopsy, his illness was associated with a very high titre of anti-double-stranded DNA antibodies, hypocomplementemia, hypergammaglobulinaemia and lymphoid hyperplasia. These features and a literature review, suggest immune-mediated lung damage in a subset of patients with UIP.

Chronic large granular lymphocytosis is a relatively common condition and comprises a clinically heterogenous group of patients. Phenotypically these can be divided into CD3+ (T cell) and CD3-(NK cell) expansions. They are characterized by a benign clinical course and a mild lymphocytosis, though a specific subgroup have a history of auto-immune disease and cytopenias. In order to develop a better understanding of the immunological abnormalities associated with this condition we examined systematically serum samples from 92 such patients for the presence of auto-antibodies, acute phase proteins and immunoglobulin levels. Auto-antibodies were found in 34% of patients and rheumatoid factor in 26%, though only half of these had active arthritis. Anti-neutrophil antibodies were negative in all cases. Quantitative immunoglobulin abnormalities were frequent with a distinct paraprotein present in three patients. The high incidence of multiple immunological abnormalities in these patients ranged from polyclonal hypergammaglobulinaemia and auto-antibodies through to monoclonal gammopathy. The aetiology of these abnormalities was unclear and undoubtedly complex, and should necessarily form part of the diagnostic investigations for all patients with persistent large granular lymphocyte expansions.

(NZB x NZW)F1(NZB/WF1) mice spontaneously develop an autoimmune disease characterized by abnormality of haemopoietic stem cells. The present study examined a possible regulatory cell interaction between NZB/WF1 and normal bone marrow cells using radiation-induced chimeras. We demonstrated that the ability of NZB/WF1 bone marrow cells to transfer the typical disease with hypergammaglobulinemia including autoantibodies into lethally irradiated normal recipients was prevented by cotransfer of bone marrow from normal CBA/J mice but not from xid CBA/N mice carrying a selective defect in B-cell function. Flow cytometric analysis revealed that the generation of NZB/WF1 cells was reduced in the mixed chimeras given CBA/J but not CBA/N bone marrow cells. Interestingly, radiation chimeras reconstituted with a mixture of NZB/WF1 bone marrow and CBA/J splenic B cells did not show elevation of serum immunoglobulin levels, although most of the spleen cells were dominated by NZB/WF1 cells. On the other hand, NZB/WF1 B cells maturated in vivo in the presence of CBA/J bone marrow or splenic B cells lost the hyper-responsiveness to lipopolysaccharide (LPS) in the autoantibody production in vitro. These results suggest that radiosensitive normal B-lineage cells have the regulatory activity to ameliorate the hypergammaglobulinemia of NZB/WF1 mice by reducing the generation of NZB/WF1 B cells and/or by correcting their hyper-responsiveness, and that NZB/WF1 mice may have a defect(s) in the regulatory cell function. In addition, CBA/J splenic B cells were shown to modulate the B-cell abnormality even when injected into non-irradiated NZB/WF1 mice manifesting autoimmunity.

Polyclonal activation of B-lymphocytes accompanies many retroviral infections. Friend derived murine immunosuppressive virus (Fd-MIV) is a non-defective murine retrovirus which was isolated from T-helper cells from mice infected with the acute transforming retrovirus Friend leukaemia complex (FLC). In contrast to FLC, Fd-MIV does not induce acute transformation of lymphoid and erythroid cells but causes immunosuppression and lymphadenopathy in adult NMRI mice. The effect of Fd-MIV infection on B-lymphocytes was studied. Fd-MIV infection led to a persistent hypergammaglobulinemy with a significant increase in the level of circulating IgG, IgM and immune complexes. In the spleen and lymph nodes, B-lymphocyte proliferation was found. Parallel to the development of hypergammaglobulinemy, autoantibodies to a variety of nuclear and other autoantigens was detected. In conclusion, the Fd-MIV infection leads to a B-lymphocyte dysfunction that has many parallels with AIDS. Furthermore, the Fd-MIV infection seems to represent an example of an autoimmune condition caused by an exogenous infectious agent.

Antibody activity in the major classes and IgG subclasses against antigens in factory humidifier water was quantified by enzyme immunoassay (EIA) in 88 subjects who were exposed at work to the output from these contaminated humidifiers. Those with work-related symptoms had significantly higher mean titres than those who were symptom free, although values overlapped. The individuals with the highest IgG antibody titres also had the highest titres of IgM and IgA antibody, and these parameters did not discriminate between those with and without symptoms any better than the IgG titre. This was also true for the IgG subclasses where activity was predominantly measured in IgG1. Quantifying the IgG antibody allowed us to demonstrate a significant correlation with years of work exposure (P less than 0.001). There was no significant association between antibody and cigarette smoking, as assessed by smoking history and confirmed objectively by serum cotinine levels. There was a significant correlation with total IgG level (P less than 0.001) suggesting that a non-specific immune enhancement may accompany the specific response. The antibody titres were followed up to 3 years after modification of the humidification systems, and during this time symptoms resolved and the antibody levels progressively fell to undetectable levels. The EIA was adapted to measure antigen at nanogram levels thus providing a rapid test for screening of humidifer water as well as a technique that may help identify the nature of the antigens involved.

Homozygous C57BL/6 nude, beige mice (B6 nu,bg) were used as recipients for the transfer of lymphoid cells from autoimmune homozygous B6 'viable motheaten' mice (B6 mev) and from either normal B6 mice (B6 wild) or B6 bg mice as controls. Surprisingly, the mev cell grafts prolonged survival of these short-living doubly immunodeficient recipients. Although the [mev----nu,bg] chimeras did not develop the mev external necrosis phenotype, they showed a hyperglobulinaemia and a significant increase of their anti-single-stranded DNA (ssDNA) antibody titres, compared to control chimeras ([bg----nu,bg] and [wild----nu,bg]). However, this hyperglobulinaemia was quite different from the mev-type hyperglobulinaemia, with poor contribution of the IgM isotype. Moreover, the anti-ssDNA antibodies were more distributed among the various Ig classes than the anti-ssDNA antibodies of the mev homozygous mice. Though the adoptive transfer of some mev-type humoral autoimmunity symptoms were achieved in this chimera model, the recipient mice did not suffer from the several other features of the mev syndrom, such as the severe pathology and the extremely high IgM serological levels.

In order to investigate the imbalance of IgG subclasses and its relationship to IgE level, 14 patients with hyper IgE syndrome (HIE syndrome) were examined for serum IgG subclasses and IgE levels and five of these patients were studied for in vitro IgE and IgG subclass production by peripheral blood lymphocytes (PBL) in response to interleukin-4 (IL-4)/interferon-gamma (IFN-gamma). Serum IgE levels were highly correlative with serum IgG4 levels (r = 0.75, P less than 0.005), but not with IgG1, IgG2 or IgG3 levels (r = 0.21, 0.43 and 0.41, respectively). In an in vitro study, recombinant IL-4 enhanced not only spontaneous IgE synthesis but also IgG4 synthesis in cultures of PBL from patients with HIE syndrome as well as in healthy donors (P less than 0.01), and the effect of recombinant IL-4 on both IgE and IgG4 synthesis was inhibited by low concentrations of recombinant IFN-gamma (P less than 0.01). The disturbed regulation of IgE and IgG4 seen in patients with hyper IgE syndrome may be caused mainly by the disturbed regulation of both cytokines.

Immunoglobulin-secreting cells were enumerated in the peripheral blood of 31 patients with multiple myeloma, nine patients with so-called benign monoclonal gammopathy, and ten patients with polyclonal hypergammaglobulinaemia or idiopathic hypogammaglobulinaemia. Immunoglobulin-secreting cells were detected by a haemolytic plaque assay using protein-A-coated erythrocytes in the presence of class- or type-specific rabbit anti-human immunoglobulin antisera. In about two-thirds of patients with multiple myeloma, cells secreting the same light-chain isotype of their serum M-protein increased in number, whereas this was not the case in the patients with so-called benign monoclonal gammopathy. Follow-up studies of immunoglobulin-secreting cells in multiple myeloma revealed that these cells increased or decreased, correlating with the severity of the disease, and alterations were more rapid than other clinical features. This plaque assay is therefore useful in evaluating the response to chemotherapy in patients with multiple myeloma.

We fractionated, by gel chromatography, sera with high IgE content from atopic subjects and five cases with the hyper-IgE syndrome, and measured the presence of IgE in high molecular weight (HMW) fractions. Two out of four asthmatics and four out of five hyper-IgE had HMW IgE. The same serum fractions gave positive results for conglutinin binding IgG (all six) and IgA (three cases) as well as C1q binding complexes (five cases). IgG auto-antibodies to IgE were also detected together with IgE in HMW fractions. Anti-F(ab)'2 activity was present in five cases (one of them negative for IgG anti-IgE). Our data indicate that complexes made of IgE and IgG anti-IgE are present mainly in patients with chronic allergic symptoms and most frequent in cases of hyper-IgE syndrome.

A complex between serum albumin and immunoglobulins was observed on immunoelectrophoresis in six patients. Two patients with multiple myeloma had monoclonal IgA-albumin complexes; one of these complexes was formed by covalent bonds and the other by non-covalent bonds. Four patients displayed non-covalent IgG-albumin complexes: of these, one had multiple myeloma, two had been treated with nitrofurantoin for prolonged periods, and one had diabetes mellitus. The IgG-albumin complex of the last patient was subjected to a detailed immunochemical analysis. The albumin-specific antibodies were isolated by affinity chromatography and analysed, using a sensitive tritium labelling technique. The antibodies were polyclonal, complexed with serum albumin through their Fab portion, and showed a high specificity for the human albumin as compared with bovine and rabbit albumins. The serum albumin of two patients displayed an abnormal behaviour in reduced SDS-polyacrylamide gel electrophoresis (PAGE). The abnormal albumins had an apparent molecular weight of 52,000 and could react with rabbit anti-human serum albumin like the normal protein. No abnormal albumin could be detected in 20 other patients' sera, including nitrofurantoin-treated patients and normal controls. These findings suggest a possible role for an altered self-component in the triggering of a specific autoimmune reaction.

The cellulose acetate electrophoretic pattern of the serum from patient Sik disclosed two distinct peaks, representing two monoclonal proteins. On immunoelectrophoresis the two M-components were found to differ in heavy chain class as well as in light chain type, IgG3(kappa) and IgA1(lambda). Serum immunoglobulin levels remained relatively constant over a period of 7 years and no clinical symptoms of a malignant deterioration occurred. It was found that the isolated M-components did not share idiotypic antigenicity. Bone marrow cells synthesizing the monoclonal proteins were identified by means of the immunofluorescent technique using isotypic as well as idiotypic antisera. Two distinct monoclonal cell populations were observed, containing either the IgG3(kappa) or the IgA1(lambda) monoclonal protein. The alpha 1-chain belonged to the VHIII subgroup, whereas the gamma 3-chain was found to be blocked. Subsequent sequence determination showed the gamma 3-chain to belong to the VHIII subgroup. It was concluded that the two M-components in the serum of patient Sik resulted from two independent neoplastic transformations.

Peripheral blood mononuclear cells (PBM) from four patients with IgG myeloma and four patients with benign monoclonal gammopathy (BMG) were stimulated with pokeweed mitogen (PWM), and the in vitro immunoglobulin production over 7 days was measured with an enzyme-linked immunosorbent assay. All myeloma patients were sufficiently treated with cytostatic drugs. Their PBM did not produce monoclonal Ig in vitro, as opposed to PBM from two patients with BMG. Unseparated PBM from myeloma patients produced smaller amounts of polyclonal Ig than unseparated cells from normal donors. However, macrophage-depleted PBM from myeloma patients produced amounts of Ig comparable to those of normal donors when autologous or allogeneic adherent cells were returned in defined numbers. T cells from three of the four myeloma patients could provide help for the Ig production by B cells from healthy donors. These results indicate that functionally normal polyclonal B cells circulate in the blood of myeloma patients. The circulating T-cell population also has no obvious defect. In contrast, blood macrophages seemed to be altered with respect to their regulating function for polyclonal Ig production. The results obtained by using cell populations from patients with BMG did not differ from those of healthy people.

Mink persistently infected with Aleutian disease virus (ADV) develop hypergammaglobulinaemia and immune complex disease. Radiolabelled antibodies from mink infected with ADV-G, DK, Pullman , and Utah I strains of ADV were reacted against all four ADV strains in radioimmunoassay (RIA). The amount of anti-ADV antibody in two equally hypergammaglobulinaemic serum pools varied from 13% (anti- Pullman ) to 57% (anti-Utah I). Serum pools from two other sources (anti-DK and anti-ADV-G), although less hypergammaglobulinaemic , had 5% and 13%, respectively, indicating that 43-95% of the Ig in the sera of mink with AD was not specific antibody to ADV structural antigens. The possibility of a general polyclonal activation of the humoral immune system is being discussed. Comparison of plateau RIA binding levels for the four serum pools against the four viral antigens suggested three patterns of reactivity: DK and Utah I reacted similarly, but Pullman and ADV-G reacted serologically different.

Sera from seventy chickens of several inbred lines were screened by cellulose acetate electrophoresis for abnormalities of immunoglobulin production. IgG levels in two sera (both from apparently healthy birds) were unusually high. The IgG proteins purified from these two sera were shown, by isoelectric focusing, to be of restricted heterogeneity.

Morphologic and immunological findings found in a patient with immunoblastic lymphadenopathy (IBL)-like T-cell lymphoma (IBL-T) are presented. Though the initial clinical features were suggestive of IBL, multiple cutaneous and visceral tumors appeared later in his course. The cutaneous lesion is considered to be unique, because the neoplastic T cells with suppressor/cytotoxic (S/C) phenotype showed focal epidermotropism, resulting in necrosis and ulceration of the overlying epidermis. An interesting feature in IBL-T is the frequent association of polyclonal hypergammaglobulinemia, yet the neoplastic T cells show S/C phenotype. Since Ia-like antigen was expressed on the neoplastic T cells, it is stressed that antigen-presenting and contrasuppressor cells should also be included in the cell populations which have a possibility to be a normal counterpart of IBL-T.

Genetic factors have been proposed to play a role in the aetiology of a monoclonal proliferation of B lymphocytes. As an additional genetic factor we postulate that a restriction in the idiotypic variability of an individual contributes to a genetic predisposition to monoclonal gammopathy. To support our hypothesis, we have examined three families with multiple occurrence of M-components for sharing of idiotypic antigenicity between the related M-components and between the M-components and the sera of unaffected relatives. Idiotypic antisera against five isolated M-components were raised in guinea-pigs and used in a radiobinding inhibition assay. In none of the three families was idiotypic cross-reactivity observed between the familial M-components. However, in a family with three members with an M-component, sera of first-degree relatives showed a higher inhibitory capacity than sera of non-related individuals when an idiotypic antiserum, raised against the M-component of proposita, was employed. Within this particular family the observed restriction in the idiotypic variability could have contributed to the multiple occurrence of M-components.

Nematospiroides dubius, in common with many other species of metazoan parasite, induces an IgG1 hypergammaglobulinaemia during the course of infection. In the present study, immune sera raised in CFLP mice by repeated infection contained 24 ng/ml IgG1 compared with a resting level of 2.4 mg/ml. IgG2a and IgG2b levels were depressed following infection from 1.5 to 0.6 mg/ml and 0.64 to 0.42 mg/ml respectively. IgM levels were unaltered by infection (0.16 mg/ml) whilst IgA levels increased from 0.7 to 1.2 mg/ml. Immunochemical fractionation of immune sera by a combination of affinity chromatography and gel filtration revealed that the anti-parasite activity of the original serum could be largely accounted for by purified IgG1 fractions as assessed by immunoprecipitin and immunofluorescence assays. Purified IgG1 was shown to react with antigenic components common to both adult homogenate and adult excretory-secretory antigen. In addition, absorption studies revealed that as much as 48% of purified IgG1 from immune serum reacted with adult N. dubius antigen. In vivo, IgG1 was the only purified immunoglobulin isotype to cause significant reduction in worm numbers in the gastrointestinal tract when administered alone, and to have any noticeable co-operative effect when administered in conjunction with immune mesenteric lymph node cells. IgG1 also caused severe stunting of worms, and promoted the adherence of peritoneal exudate cells to the worm surface in vitro. It is suggested that one mechanism by which immune mesenteric lymph-node cells exert their protective activity following cell transfer is by elevating IgG1 levels in recipient mice.

A simple rapid spot immunoprecipitate assay (SIA) is presented. The antigen--antibody reaction takes place in a field of alternating current; small amounts of specific antisera are used, and the influence of diffusion or electromobility of the antigen is avoided. Determinations of IgG, IgA and IgM in sera from healthy individuals correlated highly significantly with radial immunodiffusion (RID) results. The reaction conditions in SIA, particularly the availability of a sufficiency of specific antibodies, may permit more accurate estimates of monoclonal forms of Ig than in RID, where the combination depends on diffusion of one reactant. The precision of SIA quantitation of IgG and IgA was within +/- 10% and +/- 13% for IgM. Working ranges of the standard curves were from about 25--150 ng for G and A and 75--300 ng for IgM; least squares regression coefficients for four sets of standards on three SIA plates were 0.995 for IgG, 0.969 for IgA, and 0.986 for IgM. IgA at 7.5 ng in a 2.5 mg/l dilution was at the lower limit of demonstrability. Photometric registrations and estimates made by visual inspection compared highly significantly (P less than 0.001), differing by +/- 3%.

The serum protein SAA, which is related to the amyloid fibril protein AA, was detected by double immunodiffusion using anti-protein AA antiserum. The SAA level was elevated in 16 to 32 patients with benign monoclonal gammopathy (BMG). In addition, two BMG sera reacted with an antiserum to amyloid fibril protein of immunoglobulin light-chain type, V lambdaI (EF), and one reacted with antiamyloid protein VlambdaV (AR). The reactivity of the BMG sera with antisera to the various amyloid fibril proteins was strikingly similar to that of 35 sera from patients with myelomatosis. In the age group of 50--70 years the proportion of SAA-positive sera in BMG (53%) and myelomatosis (56%) was strikingly higher than that of the normal controls (5%). In older subjects (70--90 years), however, the frequency of SAA in BMG or myelomatosis, although increased (53%--54%), was not significantly greater than that of a control group of apparently healthy individuals (44%).

The role of H-2 genetic factors in the development of benign monoclonal gammopathy (BMG) was investigated in six H-2 congenic C57BL and BALB strains (C57BL/10.ScSn and BALB.B: H-2b; B10.D2 and BALB/c: H-2d; B10.BR and BALB.K: H-2k) during ageing. The frequencies of homogeneous immunoglobulins (H-Ig), both single and multiple, in the three C57BL strains were higher than those in the corresponding three BALB strains. No relationship was found with a particular H-2 haplotype. The most frequent H-Ig isotype within the C57BL strains was IgG2a, within BALB.B and BALB.K mice IgG3 and in BALB/c mice IgG1. Categorization of the monoclonal gammopathies (MG) on the basis of their origin showed a single transient monoclonal B-cell proliferation in 2-5% and 3-9% of the C57BL and BALB mice positive for H-Ig, respectively. Multiple myeloma or B-cell lymphoma were found to be responsible for about 1% of the paraproteinaemias in all strains. Persistent, non-progressive MG, most likely BMG, was detected in 70-81% and 39-46% of the C57BL and BALB mice positive for H-Ig, respectively. The remaining 14-24% and 50-58% of the, respectively, C57BL and BALB mice positive for H-Ig could not be evaluated in time. The H-2 haplotypes under investigation were not associated with the onset, occurrence, multiplicity, persistence or isotype of the MG developing in these H-2 congenic C57BL and BALB strains during ageing.