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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

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YSRTMCA1889 | Monkey IgA, Clone CDA2_42, Mab anti_Swine, Dog, Cat; ELISA_WB, 0.25 mg.
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(1) Integrated analysis of B‑cell and T‑cell receptors by high‑throughput sequencing reveals conserved repertoires in IgA nephropathy.[TOP]

Pubmed ID :29568935
Publication Date : //
Immunoglobulin A nephropathy (IgAN) is a type of glomerular disorder associated with immune dysregulation, and understanding B‑/T‑cell receptors (BCRs/TCRs) may be valuable for the development of specific immunotherapeutic interventions. In the present study, B and T cells were isolated from IgAN patients and healthy controls, and the composition of the BCR/TCR complementarity‑determining region (CDR)3 was analyzed by multiplex polymerase chain reaction, high‑throughput sequencing and bioinformatics. The present results revealed that the BCR/TCR CDR3 clones were expressed at very low frequencies, and the composition of clone types in patients with IgAN was skewed; the majority of clones were unique, and only 12 BCR and 228 TCR CDR3 clones were public ones, of which 16 were expressed at a significantly higher frequency in patients with IgAN (P<0.001). There were also certain conserved amino acid residues between unique clones or groups, and the residues GMDV, EQY and EQF were recurring only in the IgAN group. In addition, some VDJ gene recombinations indicated great variation between groups, including 4 high‑frequency VDJ gene recombinations in the IgAN patients (P<0.001). Immune repertoires provide novel information, and conserved BCR/TCR CDR3 clones and VDJ gene recombinations with great variation may be potential therapeutic targets for IgAN patients.

Authors : Ou Minglin, Zheng Fengping, Zhang Xinzhou, Liu Song, Tang Donge, Zhu Peng, Qiu Jingjun, Dai Yong,



(2) Characterization of sentinel node-derived antibodies from breast cancer patients.[TOP]

Pubmed ID :29382466
Publication Date : //
Autoantibodies to breast and other cancers are commonly present in cancer patients. A method to rapidly produce these anti-cancer autoantibodies in the lab would be valuable for understanding immune events and to generate candidate reagents for therapy and diagnostics. The purpose of this report is to evaluate sentinel nodes (SNs) of breast cancer patients as a source of anti-cancer antibodies. Radiotracer lymphatic mapping in 29 patients with breast cancer confirmed the identity of the SNs which provided source cells for this study. Flow cytometry demonstrated ~28% of the MNCs were B cells and ~44% of the B cells were class switched memory B cells. EBV-induced proliferation of B cells yielded tumor binding antibodies from 3 wells per 1000 but cultures were too unstable for detailed evaluations. Hybridomas generated by electrofusion produced IgG (48%), IgM (34%) and IgA (18%) antibody isotypes which were screened for binding to a panel of breast cancer cells of the major molecular subtypes. Tumor lysate binding was observed in 28% of the hybridoma clones and 10% of these bound whole tumor cells with unique binding patterns. More detailed evaluation of selected clones showed binding to the patient's own tumor. SNs are removed from more than 100,000 breast cancer patients in the US per year. Samples from these lymph nodes represent a substantial opportunity to generate anticancer antibodies.

Authors : Shukla Girja S, Pero Stephanie C, Sun Yu-Jing, Carman Chelsea L, Harlow Seth, Krag David N,



(3) 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,



(4) 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,



(5) 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,



(6) 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,



(7) 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,



(8) 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,



(9) 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,



(10) 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,