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Monkey IgA, Clone CDA2_42, Mab anti_Swine, Dog, Cat; ELISA_WB

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[#YSRTMCA1889] Monkey IgA, Clone CDA2_42, Mab anti_Swine, Dog, Cat; ELISA_WB


YSRTMCA1889 | Monkey IgA, Clone CDA2_42, Mab anti_Swine, Dog, Cat; ELISA_WB, 0.25 mg.
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(1) Monoclonal gammopathy with double M-bands: An atypical presentation on serum protein electrophoresis simulating biclonal gammopathy.[TOP]

Pubmed ID :29323083
Publication Date : //
Monoclonal gammopathies, such as multiple myeloma, typically exhibit high levels of a monoclonal immunoglobulin (M-protein), produced by a clone of abnormally proliferating B-lymphocytes and/or plasma cells. The M-protein can be evaluated by serum protein electrophoresis (SPEP), which yields a single discrete band (M-band), usually in the γ-globulin region. Rarely, two M-bands appear simultaneously at different positions during SPEP - a condition known as biclonal gammopathy, which is a result of clonal expansion of two different neoplastic cell lines. Here, we describe an atypical case of IgA-λ multiple myeloma, where double M-bands (one in β- and the other in γ-globulin region) were found during SPEP simulating biclonal gammopathy, although it was monoclonal in nature. This peculiar presentation of double M-bands in monoclonal gammopathy was attributed to polymeric forms of IgA by systematic workup. Further, we discuss how true and apparent biclonality can be distinguished by inexpensive analytical techniques in resource-constrained settings.

Authors : Bora Kaustubh, Das Umesh, Barman Bhupen, Ruram Alice Abraham,

(2) Response comparison of multiple myeloma and monoclonal gammopathy of undetermined significance to the same anti-myeloma therapy: a retrospective cohort study.[TOP]

Pubmed ID :29146225
Publication Date : //
Multiple myeloma is consistently preceded by monoclonal gammopathy of undetermined significance (MGUS), which is usually only treated by a form of anti-multiple myeloma therapy if it is causing substantial disease through deposition of secreted M proteins. However, studies comparing how MGUS and multiple myeloma plasma cell clones respond to these therapies are scarce. Biclonal gammopathy multiple myeloma is characterised by the coexistence of an active multiple myeloma clone and a benign MGUS clone, and thus provides a unique model to assess the responses of separate clones to the same anti-multiple myeloma therapy, in the same patient, at the same time. We aimed to identify how MGUS and multiple myeloma plasma cell clones responded to anti-multiple myeloma therapy in patients newly diagnosed with biclonal gammopathy multiple myeloma.

Authors : Campbell John P, Heaney Jennifer L J, Pandya Sankalp, Afzal Zaheer, Kaiser Martin, Owen Roger, Child J Anthony, Cairns David A, Gregory Walter, Morgan Gareth J, Jackson Graham H, Bunce Chris M, Drayson Mark T,

(3) Inflammation-induced IgA+ cells dismantle anti-liver cancer immunity.[TOP]

Pubmed ID :29144460
Publication Date : //
The role of adaptive immunity in early cancer development is controversial. Here we show that chronic inflammation and fibrosis in humans and mice with non-alcoholic fatty liver disease is accompanied by accumulation of liver-resident immunoglobulin-A-producing (IgA) cells. These cells also express programmed death ligand 1 (PD-L1) and interleukin-10, and directly suppress liver cytotoxic CD8 T lymphocytes, which prevent emergence of hepatocellular carcinoma and express a limited repertoire of T-cell receptors against tumour-associated antigens. Whereas CD8 T-cell ablation accelerates hepatocellular carcinoma, genetic or pharmacological interference with IgA cell generation attenuates liver carcinogenesis and induces cytotoxic T-lymphocyte-mediated regression of established hepatocellular carcinoma. These findings establish the importance of inflammation-induced suppression of cytotoxic CD8 T-lymphocyte activation as a tumour-promoting mechanism.

Authors : Shalapour Shabnam, Lin Xue-Jia, Bastian Ingmar N, Brain John, Burt Alastair D, Aksenov Alexander A, Vrbanac Alison F, Li Weihua, Perkins Andres, Matsutani Takaji, Zhong Zhenyu, Dhar Debanjan, Navas-Molina Jose A, Xu Jun, Loomba Rohit, Downes Michael, Yu Ruth T, Evans Ronald M, Dorrestein Pieter C, Knight Rob, Benner Christopher, Anstee Quentin M, Karin Michael,

(4) Regeneration of the entire human epidermis using transgenic stem cells.[TOP]

Pubmed ID :29144448
Publication Date : //
Junctional epidermolysis bullosa (JEB) is a severe and often lethal genetic disease caused by mutations in genes encoding the basement membrane component laminin-332. Surviving patients with JEB develop chronic wounds to the skin and mucosa, which impair their quality of life and lead to skin cancer. Here we show that autologous transgenic keratinocyte cultures regenerated an entire, fully functional epidermis on a seven-year-old child suffering from a devastating, life-threatening form of JEB. The proviral integration pattern was maintained in vivo and epidermal renewal did not cause any clonal selection. Clonal tracing showed that the human epidermis is sustained not by equipotent progenitors, but by a limited number of long-lived stem cells, detected as holoclones, that can extensively self-renew in vitro and in vivo and produce progenitors that replenish terminally differentiated keratinocytes. This study provides a blueprint that can be applied to other stem cell-mediated combined ex vivo cell and gene therapies.

Authors : Hirsch Tobias, Rothoeft Tobias, Teig Norbert, Bauer Johann W, Pellegrini Graziella, De Rosa Laura, Scaglione Davide, Reichelt Julia, Klausegger Alfred, Kneisz Daniela, Romano Oriana, Secone Seconetti Alessia, Contin Roberta, Enzo Elena, Jurman Irena, Carulli Sonia, Jacobsen Frank, Luecke Thomas, Lehnhardt Marcus, Fischer Meike, Kueckelhaus Maximilian, Quaglino Daniela, Morgante Michele, Bicciato Silvio, Bondanza Sergio, De Luca Michele,

(5) Characterization and use of the novel human multiple myeloma cell line MC-B11/14 to study biological consequences of CRISPR-mediated loss of immunoglobulin A heavy chain.[TOP]

Pubmed ID :29030084
Publication Date : //
The genetic abnormalities underlying multiple myeloma (MM) are notoriously complex and intraclonal heterogeneity is a common disease feature. In the current study, we describe the establishment of a monoclonal immunoglobulin A (IgA) kappa (κ) MM cell line designated MC-B11/14. Cytogenetic and fluorescence in situ hybridization analyses of the original and relapse patient samples revealed that the MM clone was nonhyperdiploid and possessed an 11;14 chromosomal translocation. The MC-B11/14 cell line, established from the relapse sample, is tetraploid and houses the t(11;14) abnormality. Given our long-standing interest in Ig function and secretion, we next used CRISPR technology to knock out IgA heavy-chain expression in the MC-B11/14 cells to assess the biological consequences of converting this cell line to one only expressing κ light chains. As expected, secretion of intact IgA was undetectable from MC-B11/14 cells. Sensitivity to pomalidomide treatment was similar between the MC-B11/14 and MC-B11/14 cells; however, MC-B11/14 cells were found to be significantly more resistant to bortezomib treatment. This study describes the establishment of a new human MM cell line tool with which to study disease biology and the use of CRISPR technology to create a potentially useful model with which to study MM light-chain escape.

Authors : Walters Denise K, Arendt Bonnie K, Tschumper Renee C, Wu Xiaosheng, Jelinek Diane F,

(6) Human Secretory IgM Emerges from Plasma Cells Clonally Related to Gut Memory B Cells and Targets Highly Diverse Commensals.[TOP]

Pubmed ID :28709802
Publication Date : //
Secretory immunoglobulin A (SIgA) enhances host-microbiota symbiosis, whereas SIgM remains poorly understood. We found that gut IgM plasma cells (PCs) were more abundant in humans than mice and clonally related to a large repertoire of memory IgM B cells disseminated throughout the intestine but rare in systemic lymphoid organs. In addition to sharing a gut-specific gene signature with memory IgA B cells, memory IgM B cells were related to some IgA clonotypes and switched to IgA in response to T cell-independent or T cell-dependent signals. These signals induced abundant IgM which, together with SIgM from clonally affiliated PCs, recognized mucus-embedded commensals. Bacteria recognized by human SIgM were dually coated by SIgA and showed increased richness and diversity compared to IgA-only-coated or uncoated bacteria. Thus, SIgM may emerge from pre-existing memory rather than newly activated naive IgM B cells and could help SIgA to anchor highly diverse commensal communities to mucus.

Authors : Magri Giuliana, Comerma Laura, Pybus Marc, Sintes Jordi, Lligé David, Segura-Garzón Daniel, Bascones Sabrina, Yeste Ada, Grasset Emilie K, Gutzeit Cindy, Uzzan Mathieu, Ramanujam Meera, van Zelm Menno C, Albero-González Raquel, Vazquez Ivonne, Iglesias Mar, Serrano Sergi, Márquez Lucía, Mercade Elena, Mehandru Saurabh, Cerutti Andrea,

(7) Human memory B cells.[TOP]

Pubmed ID :27499139
Publication Date : //
A key feature of the adaptive immune system is the generation of memory B and T cells and long-lived plasma cells, providing protective immunity against recurring infectious agents. Memory B cells are generated in germinal center (GC) reactions in the course of T cell-dependent immune responses and are distinguished from naive B cells by an increased lifespan, faster and stronger response to stimulation and expression of somatically mutated and affinity matured immunoglobulin (Ig) genes. Approximately 40% of human B cells in adults are memory B cells, and several subsets were identified. Besides IgG and IgA memory B cells, ∼50% of peripheral blood memory B cells express IgM with or without IgD. Further smaller subpopulations have additionally been described. These various subsets share typical memory B cell features, but likely also fulfill distinct functions. IgM memory B cells appear to have the propensity for refined adaptation upon restimulation in additional GC reactions, whereas reactivated IgG B cells rather differentiate directly into plasma cells. The human memory B-cell pool is characterized by (sometimes amazingly large) clonal expansions, often showing extensive intraclonal IgV gene diversity. Moreover, memory B-cell clones are frequently composed of members of various subsets, showing that from a single GC B-cell clone a variety of memory B cells with distinct functions is generated. Thus, the human memory B-cell compartment is highly diverse and flexible. Several B-cell malignancies display features suggesting a derivation from memory B cells. This includes a subset of chronic lymphocytic leukemia, hairy cell leukemia and marginal zone lymphomas. The exposure of memory B cells to oncogenic events during their generation in the GC, the longevity of these B cells and the ease to activate them may be key determinants for their malignant transformation.

Authors : Seifert M, Küppers R,

(8) Scarcity of autoreactive human blood IgA memory B cells.[TOP]

Pubmed ID :27469325
Publication Date : //
Class-switched memory B cells are key components of the "reactive" humoral immunity, which ensures a fast and massive secretion of high-affinity antigen-specific antibodies upon antigenic challenge. In humans, IgA class-switched (IgA ) memory B cells and IgA antibodies are abundant in the blood. Although circulating IgA memory B cells and their corresponding secreted immunoglobulins likely possess major protective and/or regulatory immune roles, little is known about their specificity and function. Here, we show that IgA and IgG memory B-cell antibodies cloned from the same healthy humans share common immunoglobulin gene features. IgA and IgG memory antibodies have comparable lack of reactivity to vaccines, common mucosa-tropic viruses and commensal bacteria. However, the IgA memory B-cell compartment contains fewer polyreactive clones and importantly, only rare self-reactive clones compared to IgG memory B cells. Self-reactivity of IgAs is acquired following B-cell affinity maturation but not antibody class switching. Together, our data suggest the existence of different regulatory mechanisms for removing autoreactive clones from the IgG and IgA memory B-cell repertoires, and/or different maturation pathways potentially reflecting the distinct nature and localization of the cognate antigens recognized by individual B-cell populations.

Authors : Prigent Julie, Lorin Valérie, Kök Ayrin, Hieu Thierry, Bourgeau Salomé, Mouquet Hugo,

(9) Frequent Use of the IgA Isotype in Human B Cells Encoding Potent Norovirus-Specific Monoclonal Antibodies That Block HBGA Binding.[TOP]

Pubmed ID :27355511
Publication Date : //
Noroviruses (NoV) are the most common cause of non-bacterial acute gastroenteritis and cause local outbreaks of illness, especially in confined situations. Despite being identified four decades ago, the correlates of protection against norovirus gastroenteritis are still being elucidated. Recent studies have shown an association of protection with NoV-specific serum histo-blood group antigen-blocking antibody and with serum IgA in patients vaccinated with NoV VLPs. Here, we describe the isolation and characterization of human monoclonal IgG and IgA antibodies against a GI.I NoV, Norwalk virus (NV). A higher proportion of the IgA antibodies blocked NV VLP binding to glycans than did IgG antibodies. We generated isotype-switched variants of IgG and IgA antibodies to study the effects of the constant domain on blocking and binding activities. The IgA form of antibodies appears to be more potent than the IgG form in blocking norovirus binding to histo-blood group antigens. These studies suggest a unique role for IgA antibodies in protection from NoV infections by blocking attachment to cell receptors.

Authors : Sapparapu Gopal, Czakó Rita, Alvarado Gabriela, Shanker Sreejesh, Prasad B V Venkataram, Atmar Robert L, Estes Mary K, Crowe James E,

(10) Characterization of NF-κB Reporter U937 Cells and Their Application for the Detection of Inflammatory Immune-Complexes.[TOP]

Pubmed ID :27232500
Publication Date : //
Our study tested the hypothesis that immunoglobulins differ in their ability to activate the nuclear factor-κB pathway mediated cellular responses. These responses are modulated by several properties of the immune complex, including the ratio of antibody isotypes binding to antigen. Immunoassays allow the measurement of antigen specific antibodies belonging to distinct immunoglobulin classes and subclasses but not the net biological effect of the combination of these antibodies. We set out to develop a biosensor that is suitable for the detection and characterization of antigen specific serum antibodies. We genetically modified the monocytoid U937 cell line carrying Fc receptors with a plasmid encoding NF-κB promoter-driven GFP. This clone, U937-NF-κB, was characterized with respect to FcR expression and response to solid-phase immunoglobulins. Human IgG3, IgG4 and IgG1 induced GFP production in a time- and dose-dependent manner, in this order of efficacy, while IgG2 triggered no activation at the concentrations tested. IgA elicited no response alone but showed significant synergism with IgG3 and IgG4. We confirmed the importance of activation via FcγRI by direct stimulation with monoclonal antibody and by competition assays. We used citrullinated peptides and serum from rheumatoid arthritis patients to generate immune complexes and to study the activation of U937-NF-κB, observing again a synergistic effect between IgG and IgA. Our results show that immunoglobulins have distinct pro-inflammatory potential, and that U937-NF-κB is suitable for the estimation of biological effects of immune-complexes, offering insight into monocyte activation and pathogenesis of antibody mediated diseases.

Authors : Kecse-Nagy Csilla, Szittner Zoltán, Papp Krisztián, Hegyi Zoltán, Rovero Paolo, Migliorini Paola, Lóránd Veronika, Homolya László, Prechl József,