[Alpha heavy chain disease. Molecular analysis of a new case].

The NH2-terminal structure of serum abnormal protein, as well as the sequence of the corresponding mRNA, were determined in a new case of alpha heavy chain disease. The patient presented with typical clinical features of the disease. Intestinal and mesenteric lymphoplasmic infiltration was monoclonal as assessed by the study of the configuration of heavy and light chain genes.

A human myeloma IgA with a hybrid heavy chain resulting from putative somatic gene conversion.

A human monoclonal IgA1-IgA2 lambda hybrid molecule was detected in a myeloma patient homozygous for the A2m(1) allotype during a systematic study of monoclonal IgA with subclass-specific monoclonal antibodies (mAb) and the lectin jacalin. This monoclonal immunoglobulin (GAU) reacted with both, although not with all, anti-alpha 1 and anti-alpha 2 mAb. Its heavy (H) chain contained an alpha 1 hinge region as shown by jacalin reactivity, the presence of disulfide-linked H and light chains in spite of its belonging to the IgA2m(1) allotype and amino acid composition of the isolated hinge region.

H chain V region sequences of three human monoclonal IgM with anti-myelin-associated glycoprotein activity.

The amino acid sequence corresponding to the V region H chain gene used by three monoclonal IgM directed to the myelin-associated glycoprotein (MAG) is presented. They all belonged to the VHIII variability subgroup, but each may well represent a new member of this family inasmuch as their homology with previously sequenced VHIII genes was less than 80%. Strikingly, there was no greater homology between the H chain V regions of the anti-MAG IgM.

A new extra sequence at the amino terminal of a mu heavy chain disease protein (DAG).

The primary structure of a human mu heavy chain (DAG) protein is described. The native protein is a circular decamer with a molecular weight (Mr) of 500 kDa, each decamer being constituted of the constant domains C mu 2, C mu 3 and C mu4 and interlinked by 15 disulfide bridges. At its NH2-terminal each monomeric chain starts with an "extra sequence".

Peripheral polyneuropathies associated with monoclonal IgM. Antibody activity of monoclonal IgM and therapeutic implications.

Monoclonal IgM from patients with peripheral neuropathy react in nearly 80% of the cases with some components of myelin. The main target is myelin associated glycoprotein (50% of the cases); several types of glycolipids or gangliosides have been identified as the reactive antigen in the other cases. Anti-MAG IgM share little cross reactive idiotopes.

Multiple mutations in the variable region of the kappa light chains of three monoclonal human IgM with anti-myelin-associated glycoprotein activity.

Human monoclonal IgM having an antibody activity directed to myelin-associated glycoprotein have distinctive features. Amino-terminal sequence of light and heavy chains from 6 IgM kappa that we have previously studied indicated that heavy chains belong to the VHIII subgroup, whereas light chains belong to 3 different subgroups of variability (V kappa I 2, V kappa II 1, and V kappa IV 3). We report here the complete sequence of the variable domain of 3 L chains: 2 V kappa IV and 1 V kappa II subgroups.

The productive gene for alpha-H chain disease protein MAL is highly modified by insertion-deletion processes.

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).

Genomic alterations in a case of alpha heavy chain disease leading to the generation of composite exons from the JH region.

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.

Expression of a public idiotype by human monoclonal IgM directed to myelin-associated glycoprotein and characterization of the variability subgroup of their heavy and light chains.

Most studies using rabbit or mouse antisera failed to detect CRI between human IgM directed to MAG. We show here that 9 of 10 such IgM express a public CRI as defined by a nonhuman primate antiserum. Shared idiotype is likely involved in (or close to) the combining site of those IgM since antiidiotypic serum inhibited the binding of IgM to MAG and reacted with IgM having different variable regions of light and heavy chains.

Structural studies of the asparagine-linked sugar chains of two immunoglobulin M's purified from a patient with Waldenström's macroglobulinemia.

The structures of the sugar chains present in two human monoclonal IgM molecules purified from the serum of a patient with Waldenström's macroglobulinemia have been determined. The asparagine-linked sugar chains were liberated as oligosaccharides by hydrazinolysis and labeled by reduction with NaB3H4 after N-acetylation. Their structures were studied by serial lectin column chromatography and sequential exoglycosidase digestion in combination with methylation analysis.

Jacalin: a new laboratory tool in immunochemistry and cellular immunology.

In recent years, a new lectin--jacalin--has raised the interest of immunologists because of its original properties with respect to human immunoglobulins and lymphocytes. Its structure and carbohydrate binding specificity are now well documented, and it can be purified easily from jackfruit seeds by ion exchange or affinity chromatography. The binding and precipitating specificities of jacalin with heavy chains of human immunoglobulins allow its use as a diagnostic (IgA subclass typing) and preparative tool (purification of IgA and IgD, removal of IgA from biologic samples and preparations).

Jacalin, the human IgA1 and IgD precipitating lectin, also binds IgA2 of both allotypes.

The lectin jacalin from jackfruit seeds shows a human IgA-subclass specificity by gel precipitation and Western blotting. However, its reactivity with IgA2 is a matter of controversy. We further studied the immunoglobulin isotype specificity of jacalin by affinity chromatography with myeloma sera and by inhibition of jacalin binding to solid-phase IgA1 by purified monoclonal immunoglobulins.

Protein Rou. A human IgA hybrid.

Protein Rou is a human IgA2 myeloma protein that carries the isoallotype marker n A2m(2). Partial amino acid sequence of its H chain (alpha) shows that the hinge region and the CH2 domain are homologous to alpha 2-chain and the CH1 and the CH3 domains homologous to alpha 1. Moreover, the CH1 domain contains the H-L disulfide bond identical to alpha 1.

Analysis of the domain specificity of various murine anti-human IgM monoclonal antibodies differing in human B lymphocyte signaling activity.

The domain binding specificity of 19 murine anti-human IgM monoclonal antibodies (MoAbs) that have shown considerable heterogeneity in the transduction of stimulatory and inhibitory signals to B lymphocytes was evaluated by competition radioimmunoassays. Through the use of: (i) enzymatic fragments of IgM which each encompass more than a single CH domain, i.e.

Characterization of jacalin, the human IgA and IgD binding lectin from jackfruit.

The lectin jacalin from the jackfruit Artocarpus heterophyllus reacts by precipitation and western blotting with human IgA1 and IgD but not with IgA2 (nor IgG and IgM). However, it weakly binds IgA2 as shown by affinity chromatography and competitive ELISA. Predominantly reactive carbohydrates are D-galactose and N-acetyl D-galactosamine.

Detection of cross-reactive determinants shared by human monoclonal IgM reacting with myelin-associated glycoprotein.

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.

The molecular organization of the protein HC-IgA complex (HC-IgA).

Complexes of protein HC and monoclonal IgA1 or IgA2 or polyclonal IgA were isolated from human blood plasma. Dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting showed that all complexes contain three types of chains: two light immunoglobulin chains, one regular IgA alpha-chain, and one chain with Mr = 90,000 carrying both alpha-chain and protein HC epitopes. The complexes were split into Fab alpha and Fc alpha fragments by bacterial IgA proteases.

The amino acid sequence of a lambda light chain presenting abnormal physicochemical and antigenic features.

The amino acid sequence of the light chain of a human monoclonal IgA1 (Mem) was established, in part by analogy with already known sequences. By homology its variable part was shown to belong to the V lambda I subgroup while the isotype-associated amino acid residues characterized it as Mcg+, Kern+ and Oz-. The normal primary structure of this chain was in contrast to its abnormal physical and antigenic properties: (a) its apparent molecular mass estimated by SDS/polyacrylamide gel electrophoresis, by gel filtration chromatography and by gradient ultracentrifugation was found to be lower by approximately equal to 10% than the values (23.

An anti-human mu chain monoclonal antibody: use for detection of IgM antibodies to Toxoplasma gondii by reverse immunosorbent assay.

A precipitating anti-human mu chain monoclonal antibody (designated Tibi 82 McAb) was produced by the cell fusion technique. This McAb (isotype: IgG1 kappa) reacted by radioimmunoassay with all 10 human IgM proteins tested. In contrast, no reactivity was observed with IgG, IgA, IgE, lambda and kappa chains.

The primary structure of mu-chain-disease protein BOT. Peculiar amino-acid sequence of the N-terminal 42 positions.

The complete primary structure of the mu heavy-chain disease (mu-HCD) protein BOT has been determined. The monomeric HCD-mu-chain consists of 391 amino-acid residues, lacking the VH and mu CH1 domains but including the entire CH2, CH3 and CH4 domains (349 residues). The sequence of the preceding 42 N-terminal residues which we designate as the "pre-C-part" presents no homology to any known variable or constant immunoglobulin sequence, but contains an internal homology of positions 10-19 to positions 20-29.

Biochemical and biosynthetic studies of a crystallizable human gamma 1 heavy-chain disease protein.

We have studied the structure of a crystallizable gamma 1 heavy-chain disease protein that lacks the entire VH and C gamma 1 domains. The protein starts within the hinge region at aspartic acid 221 (Eu numbering). The native protein is a disulphide-linked dimer with an apparent molecular weight of 52,000, consistent with the biochemical data obtained on the whole protein and its cyanogen bromide fragments.

Crystals of the human heavy chain disease protein Riv and human Fc fragment are isomorphous: further evidence for conformational flexibility in the hinge region of immunoglobulins.

Protein Riv is a human gamma 1 heavy chain disease immunoglobulin variant with a deletion of the entire VH and CH1 domains and consisting of most of the hinge region plus the CH2 and CH3 domains. Crystals of this protein are orthorhombic, belonging to the space group P2(1)2(1)2(1), with a = 80.1 A, b = 145.

[Light chain or monoclonal immunoglobulin deposition disease: physiopathogenic concepts].

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.

Detection of J chain in lymphomas and related disorders.

Lymph node specimens from 125 patients with malignant lymphomas and related disorders were studied by immunoperoxidase procedure for the presence of intracytoplasmic immunoglobulin (CIg) and J chain CIg staining was present in 22/24 cases of lymphoplasmacytic-lymphoplasmacytoid lymphomas, and in 10/10 cases of extramedullary plasmacytomas and myelomas. In the majority of these cases J chain could be demonstrated in plasmacytoid or neoplastic plasma cells. In 21/36 cases of immunoblastic lymphomas, intracytoplasmic Ig staining was present.

Synthesis of abnormal heavy and light chains in multiple myeloma with visceral deposition of monoclonal immunoglobulin.

In a patient treated for IgA kappa myeloma, bone marrow relapse and a sharp drop in the serum IgA level paralleled tissue deposition of non-amyloid material reactive with anti-kappa anti-alpha sera in immunofluorescence studies of kidney and liver biopsies. Clinical manifestations were progressive renal failure with nephrotic syndrome, with both tubular and glomerular lesions (including nodular glomerulosclerosis), hepatomegaly, cardiac and neurological symptoms. Biosynthesis experiments showed the production of alpha chains diminished in length by about one domain which were rapidly degraded predominantly after secretion and of two species of light chains; normal-sized light chains which assembled with alpha chains and abnormally short ones which were secreted as free light chains.