The selection of mature B cells is critically dependent on the expression level of the co-receptor CD19

Muenchow, Lilly von; Engdahl, Corinne; Karjalainen, Klaus; Rolink, Antonius

doi:10.1016/j.imlet.2014.01.011

Cited by 12 publications

(11 citation statements)

References 26 publications

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“…To study HSCs, a NUP98-HOXB4 HSC (NH-HSC) line was generated from C57BL/6 mice following the protocol established by Sauvageau et al ( 36 ) and subsequently optimized by Ruedl et al ( 37 ). The NH-HSC line obtained following this protocol was confirmed to display the surface phenotype: CD45 + Lin − c-kit + Sca-1 + CD11c − CD19 − B220 − CD4 − CD8 − and to be capable of successfully re-constituting all hematopoietic lineages in sub-lethally irradiated mice ( 38 ). For the purposes of this study, NH-HSCs were maintained in SF-IMDM (Gibco) supplemented with 5% forward light scatter (FCS) (Gibco), 3% v/v IL-6-containing supernatant, 0.1 µg/ml SCF and 0.2% v/v Ciproxin ® (Bayer Pharmaceutical) at 37°C [as described in Ref.…”

Section: Methodsmentioning

confidence: 93%

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DN2 Thymocytes Activate a Specific Robust DNA Damage Response to Ionizing Radiation-Induced DNA Double-Strand Breaks

et al. 2018

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For successful bone marrow transplantation (BMT), a preconditioning regime involving chemo and radiotherapy is used that results in DNA damage to both hematopoietic and stromal elements. Following radiation exposure, it is well recognized that a single wave of host-derived thymocytes reconstitutes the irradiated thymus, with donor-derived thymocytes appearing about 7 days post BMT. Our previous studies have demonstrated that, in the presence of donor hematopoietic cells lacking T lineage potential, these host-derived thymocytes are able to generate a polyclonal cohort of functionally mature peripheral T cells numerically comprising ~25% of the peripheral T cell pool of euthymic mice. Importantly, we demonstrated that radioresistant CD44+ CD25+ CD117+ DN2 progenitors were responsible for this thymic auto-reconstitution. Until recently, the mechanisms underlying the radioresistance of DN2 progenitors were unknown. Herein, we have used the in vitro “Plastic Thymus” culture system to perform a detailed investigation of the mechanisms responsible for the high radioresistance of DN2 cells compared with radiosensitive hematopoietic stem cells. Our results indicate that several aspects of DN2 biology, such as (i) rapid DNA damage response (DDR) activation in response to ionizing radiation-induced DNA damage, (ii) efficient repair of DNA double-strand breaks, and (iii) induction of a protective G1/S checkpoint contribute to promoting DN2 cell survival post-irradiation. We have previously shown that hypoxia increases the radioresistance of bone marrow stromal cells in vitro, at least in part by enhancing their DNA double-strand break (DNA DSB) repair capacity. Since the thymus is also a hypoxic environment, we investigated the potential effects of hypoxia on the DDR of DN2 thymocytes. Finally, we demonstrate for the first time that de novo DN2 thymocytes are able to rapidly repair DNA DSBs following thymic irradiation in vivo.

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Section: Methodsmentioning

confidence: 93%

“…For the purposes of this study, NH-HSCs were maintained in SF-IMDM (Gibco) supplemented with 5% forward light scatter (FCS) (Gibco), 3% v/v IL-6-containing supernatant, 0.1 µg/ml SCF and 0.2% v/v Ciproxin ® (Bayer Pharmaceutical) at 37°C [as described in Ref. ( 38 )], in either normoxia (21% O 2 ) or hypoxia (5% O 2 ).…”

Section: Methodsmentioning

confidence: 99%

DN2 Thymocytes Activate a Specific Robust DNA Damage Response to Ionizing Radiation-Induced DNA Double-Strand Breaks

et al. 2018

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“…Moreover, an increased BCR signaling, as shown above for Dkk3 2/2 B cells, could lead to altered B cell development, including an altered BCR editing and therewith an altered expression of the l L chain (32,33). Therefore, we analyzed whether the ratio of k to l L chainexpressing B cells is changed in Dkk3 2/2 mice on the protein level 2) mice, mixed at a ratio of 1:1, and transferred to either wt.Rag2 2/2 or Dkk3 2/2 Rag2 2/2 mice.…”

Section: Dkk3 May Contribute To the Control Of Bcr Signalingmentioning

confidence: 99%

Dickkopf-3 Acts as a Modulator of B Cell Fate and Function

Ludwig

Federico

Prokosch

et al. 2015

The Journal of Immunology

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The mechanisms responsible for the generation of a mature B1 and B2 cell compartment are still poorly understood. In this study, we demonstrated that absence of Dickkopf-3 (DKK3) led to changes in the composition of the B cell compartment, which were due to an altered development and maintenance program of B cells. Development of B2 cells was impaired at the pre- and immature B cell stage, resulting in decreased numbers of follicular B cells in adult DKK3-deficient mice. Furthermore, DKK3 limited B1 cell self-maintenance in the periphery, by decreasing the survival and proliferation behavior of B1 cells. DKK3 may act via the BCR signaling pathway, as Ca2+ influx upon BCR stimulation was increased and SiglecG, a molecule shown to inhibit Calcium signaling, was downregulated in the absence of DKK3. DKK3-deficient mice exhibited altered Ab responses and an increased secretion of the cytokine IL-10. Additionally, DKK3 limited autoimmunity in a model of systemic lupus erythematosus. In summary, we identified DKK3 as a novel modulator interfering with B cell fate as well as the maintenance program of B cells, leading to changes in B cell immune responses.

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“…The therapeutic functions can be emphasized by targeting certain surface Ags of lymphocytes (CD40 [10,11], CD20 [12–14], CD19 [15, 16], CD73 [17, 18]), mediating immune checkpoints (CTLA-4 [19], PD-1 [20, 21]), blocking the bind of specific ligands, perturbing the signaling pathways (EGFR [22, 23], HER2 [24, 25]), and other direct-targeted functions. In combination with conventional cancer therapies, Ab-based therapies that target these factors can stimulate anti-tumor response and improve clinical efficacy.…”

Section: Positive Effect Of B Lymphocytes On the Immune Systemmentioning

confidence: 99%

Positive and negative functions of B lymphocytes in tumors

et al. 2016

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Accumulating evidence indicated that B lymphocytes exerted complex functions in tumor immunity. On the one hand, B lymphocytes can inhibit tumor development through antibody generation, antigen presentation, tumor tissue interaction, and direct killing. On the other hand, B lymphocytes have tumor-promoting functions. A typical type of B lymphocytes, termed regulatory B cells, is confirmed to attenuate immune response in a tumor environment. In this paper, we summarize the current understanding of B-cell functions in tumor immunology, which may shed light on potential therapeutic strategies against cancer.

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The selection of mature B cells is critically dependent on the expression level of the co-receptor CD19

Cited by 12 publications

References 26 publications

DN2 Thymocytes Activate a Specific Robust DNA Damage Response to Ionizing Radiation-Induced DNA Double-Strand Breaks

DN2 Thymocytes Activate a Specific Robust DNA Damage Response to Ionizing Radiation-Induced DNA Double-Strand Breaks

Dickkopf-3 Acts as a Modulator of B Cell Fate and Function

Positive and negative functions of B lymphocytes in tumors

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