Parietal cell autoantigens involved in neonatal thymectomy-induced murine autoimmune gastritis. Studies using monoclonal autoantibodies

Mori, Yumiko; Fukuma, Kanzo; Adachi, Yoshifumi; Shigeta, Katsuyoshi; Kannagi, Reiji; Tanaka, Hiromu; Sakai, Masahiko; Kuribayashi, Kagemasa; Uchino, Haruto; Masuda, Tohru

doi:10.1016/0016-5085(89)90072-3

Cited by 58 publications

(37 citation statements)

References 16 publications

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“…Cryosections (10 -20 m) were fixed with cold acetone for 5 min, treated with 0.05% Tween 20-PBS containing 1% BSA and 5% mouse serum, and stained with the following Abs: biotin anti-H ϩ / K ϩ -ATPase (1H9) (12), biotin anti-CD3, FITC anti-B220, anticomplement receptor 1 (CR1), anti-peripheral node adressin (PNAd), antisyndecan-1 (BD PharMingen, San Diego, CA), anti-platelet endothelial cell adhesion molecule-1 (PECAM-1; Caltag, Burlingame, CA), anti-ER-TR7 (Serotec, Oxford, U.K.), anti-Mac-1 (Immunotech, Luminy, France), biotin anti-CXC chemokine ligand 13 (CXCL13), biotin anti-CC chemokine ligand 21 (CCL21) (R&D Systems, Minneapolis, MN), FITC antimouse IgM, PE anti-mouse IgD (Southern Biotechnology, Birmingham, AL), or FITC anti-mouse IgG (Jackson ImmunoResearch Laboratories, West Grove, PA). PE anti-rat IgG Ab (Caltag), biotin anti-mouse IgM Ab (BD PharMingen), PE streptavidin, and APC streptavidin (Molecular Probes, Eugene, OR) were used as the secondary reagents.…”

Section: Immunohistochemistrymentioning

confidence: 99%

Th1-Biased Tertiary Lymphoid Tissue Supported by CXC Chemokine Ligand 13-Producing Stromal Network in Chronic Lesions of Autoimmune Gastritis

Katakai

Hara

Sugai

et al. 2003

The Journal of Immunology

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Secondary lymphoid tissue is developmentally programmed and characterized by well-ordered compartmentalization of lymphocyte subsets and specialized stromal cells supporting the tissue architecture. By contrast, tertiary lymphoid tissue is defined as that induced in ectopic sites by inflammation, although its immunological role is largely unknown. In this study, we characterize the lymphoid tissue induced in the chronic lesion of murine autoimmune gastritis (AIG). Within the lymphoid cluster in the gastric mucosa, there is a clear segregation of T and B cells. Follicle-like B cell areas are always located on the luminal side of the mucosa, while T cells are located in the basal part. A typical lymphoid reticular network and follicular dendritic cells support the structure. Importantly, complement receptor 1+ follicular dendritic cells within the follicle express a B cell homing chemokine, CXC chemokine ligand 13. The number and size of the clusters correlate with the age of the mice and the serum autoantibody titer, suggesting the functional importance of the clusters in local Ab production, although involvement of the autoantibody in the disease progression is still unclear. AIG gastric lesions are known to constitute a Th1-biased, memory T cell-dependent immunomicroenvironment. The expression pattern of cytokines, including lymphotoxin-β, and chemokines in the AIG stomach is consistent with this observation. Taken together, these facts suggest that, during the chronic phase of autoimmunity, long-lasting lymphocyte infiltration probably induces a unique tertiary lymphoid tissue that has a function distinct from that of regional lymph nodes. These neolymphoid tissues may maintain the local self reactivity supporting the vicious cycle of Th1-type reaction as well as autoantibody production.

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Section: Immunohistochemistrymentioning

confidence: 99%

Th1-Biased Tertiary Lymphoid Tissue Supported by CXC Chemokine Ligand 13-Producing Stromal Network in Chronic Lesions of Autoimmune Gastritis

Katakai

Hara

Sugai

et al. 2003

The Journal of Immunology

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“…Samples were separated on a 10% polyacrylamide gel under reducing conditions. The band indicated with an asterisk in lane 4 is derived from the peptide N-glycosidase F enzyme preparation gastritis, induced by neonatal thymectomy, as well as by monoclonal antibodies derived from these mice [44]. We have recently shown that these monoclonal autoantibodies are indeed directed against the 95-kDa a-subunit or the 60-90-kDa P-subunit of the gastric proton pump [45].…”

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confidence: 99%

Monoclonal antibodies specific for the core protein of the β‐subunit of the gastric proton pump (H⁺/K⁺ ATPase)

Jones

Toh

Pettitt

et al. 1991

European Journal of Biochemistry

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The gastric H+/K+-transporting adenosine triphosphatase ( H + / K + ATPase) (proton pump) consists of a catalytic a-subunit and a recently proposed 60 -90-kDa glycoprotein p-subunit. Using dog gastric membranes as the antigen, we have produced two murine monoclonal antibodies, 4F11 (IgG1) and 3A6 (IgA), which are specific for the 60 -90-kDa glycoprotein.The monoclonal antibodies (1) specifically stained the cytoplasm of unfixed and formalin-fixed dog gastric parietal cells; (2) specifically reacted by ELISA with gastric tubulovesicular membranes; (3) recognised epitopes located on the luminal face of parietal cell tubulovesicular membranes, the site of the proton pump, by immunogold electron microscopy; (4) immunoblotted a 60 ~ 90-kDa molecule from tubulovesicular membranes and a 35-kDa component from peptide N-glycosidase-F-treated membrane extracts ; ( 5 ) immunoblotted the 60 ~ 90-kDa parietal cell autoantigen associated with autoimmune gastritis and pernicious anemia, purified by chromatography on parietal cell autoantibody-or tomato-lectin -Sepharose 4B affinity columns, and the 35-kDa protein core of this autoantigen; this autoantigen has amino acid sequence similarity to the p-subunit of the related Na+/K+-transporting adenosine triphosphatase (Na+/K+ ATPase) [Toh et al. (1990) Proc. Nut1 Acad. Sci. 87, 6418-64221; (6) co-precipitated a molecule of 95 kDa with the 60 -90-kDa molecule from 2sI-labelled detergent extracts of dog tubulovesicular membranes; and (7) co-purified the catalytic a-subunit of the H '/K + ATPase with the 60 -90-kDa molecule by immunoaffinity chromatography of tubulovesicular membrane extracts on a monoclonal antibody 3A6-Sepharose 4B column, indicating a physical association between the two molecules.These results provide further evidence that the 60 ~ 90-kDa glycoprotein is the p-subunit of the gastric H + / K + ATPase. We conclude that the monoclonal antibodies specifically recognise luminal epitopes on the 35-kDa core protein of the 60-90-kDa p-subunit of the gastric proton pump, a major target molecule in autoimmune gastritis and pernicious anaemia. These monoclonal antibodies will be valuable probes to study the structure and function of this associated p-subunit, as well as the ontogeny of the gastric proton pump.The parietal cells of the gastric mucosa are highly specialised for the secretion of hydrochloric acid into the stomach. Resting (non-secreting) parietal cells contain abundant smooth cytoplasmic vesicles called tubulovesicles. Upon stimulation by a variety of ligands e.g. gastrin, parietal cells undergo extensive morphological transformation resulting in hydrochloric acid secretion. These changes include an extensive reduction in the tubulovesicular membranes of the cytoplasm together with the appearance of intracellular secretory canaliculi [I, 21. Abbreviutions. H + / K + ATPase, H+/K+-transporting adenosine triphosphatase; Na+/K+ ATPase, Na+/K+-transporting adenosine triphosphatase; FITC, fluorescein isothiocyanate.Enzymes. H + / K + ATPase ( EC 3.6.1.3); Na+/K+ A...

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“…The monoclonal antibodies lH9 and 2B6, which are specific for the cr-and @subunits of the gastric H + /K ' -ATPase, respectively, were derived from mice with autoimmune gastritis induced by neonatal thymectomy [14].…”

Section: Methodsmentioning

confidence: 99%

“…2C). In contrast, a monoclonal antibody (lH9) specific for the (Ysubunit [9,14] reacted with the gastric H + /K+ -ATPase preparation only (Fig. 2B).…”

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The β‐subunit of the gastric H⁺/K⁺‐ATPase can occur without the α‐subunit

Baldwin¹

1990

FEBS Letters

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Parietal cell autoantigens involved in neonatal thymectomy-induced murine autoimmune gastritis. Studies using monoclonal autoantibodies

Cited by 58 publications

References 16 publications

Th1-Biased Tertiary Lymphoid Tissue Supported by CXC Chemokine Ligand 13-Producing Stromal Network in Chronic Lesions of Autoimmune Gastritis

Th1-Biased Tertiary Lymphoid Tissue Supported by CXC Chemokine Ligand 13-Producing Stromal Network in Chronic Lesions of Autoimmune Gastritis

Monoclonal antibodies specific for the core protein of the β‐subunit of the gastric proton pump (H⁺/K⁺ ATPase)

The β‐subunit of the gastric H⁺/K⁺‐ATPase can occur without the α‐subunit

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Parietal cell autoantigens involved in neonatal thymectomy-induced murine autoimmune gastritis. Studies using monoclonal autoantibodies

Cited by 58 publications

References 16 publications

Th1-Biased Tertiary Lymphoid Tissue Supported by CXC Chemokine Ligand 13-Producing Stromal Network in Chronic Lesions of Autoimmune Gastritis

Th1-Biased Tertiary Lymphoid Tissue Supported by CXC Chemokine Ligand 13-Producing Stromal Network in Chronic Lesions of Autoimmune Gastritis

Monoclonal antibodies specific for the core protein of the β‐subunit of the gastric proton pump (H+/K+ ATPase)

The β‐subunit of the gastric H+/K+‐ATPase can occur without the α‐subunit

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Product

Resources

About

Monoclonal antibodies specific for the core protein of the β‐subunit of the gastric proton pump (H⁺/K⁺ ATPase)

The β‐subunit of the gastric H⁺/K⁺‐ATPase can occur without the α‐subunit