Reprint of: Environments of B cell development

Tsuneto, Motokazu; Kajikhina, Ekaterina; Seiler, Katharina; Reimer, Andreas S.; Tornack, Julia; Bouquet, Corinne; Simmons, Szandor; Knoll, Marko; Wolf, Ingrid; Tokoyoda, Koji; Hauser, Anja E.; Hara, Takahiro; Tani-ichi, Shizue; Ikuta, Koichi; Grün, Joachim R.; Grützkau, Andreas; Engels, Niklas; Wienands, Jürgen; Yanagisawa, Yuki; Ohnishi, Kouhei; Melchers, Fritz

doi:10.1016/j.imlet.2014.05.005

Cited by 3 publications

(1 citation statement)

References 36 publications

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“…Upon recognition of foreign antigens, mature naive B lymphocytes are activated, leading to the production of short-lived plasma cells, followed by their proliferation and differentiation into memory B-lymphocytes and long-lived plasma cells for durable Ig production [ 39 , 40 ]. Along these different steps, B-lymphocytes respond to diverse signals or survival/proliferation factors, including BAFF/APRIL, BCR, IL6, VEGF, EGF, and IGF-1 [ 39 ].…”

Section: Cell Surface Markersmentioning

confidence: 99%

Targeted Therapies in Adult B-Cell Malignancies

Rossi

2015

BioMed Research International

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B-lymphocytes are programmed for the production of immunoglobulin (Ig) after antigen presentation, in the context of T-lymphocyte control within lymphoid organs. During this differentiation/activation process, B-lymphocytes exhibit different restricted or common surface markers, activation of cellular pathways that regulate cell cycle, metabolism, proteasome activity, and protein synthesis. All molecules involved in these different cellular mechanisms are potent therapeutic targets. Nowadays, due to the progress of the biology, more and more targeted drugs are identified, a situation that is correlated with an extended field of the targeted therapy. The full knowledge of the cellular machinery and cell-cell communication allows making the best choice to treat patients, in the context of personalized medicine. Also, focus should not be restricted to the immediate effects observed as clinical endpoints, that is, response rate, survival markers with conventional statistical methods, but it should consider the prediction of different clinical consequences due to other collateral drug targets, based on new methodologies. This means that new reflection and new bioclinical follow-up have to be monitored, particularly with the new drugs used with success in B-cell malignancies. This review discussed the principal aspects of such evident bioclinical progress.

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Section: Cell Surface Markersmentioning

confidence: 99%

Targeted Therapies in Adult B-Cell Malignancies

Rossi

2015

BioMed Research International

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Cytokine‐Producing B Cells Promote Immune‐Mediated Bile Duct Injury in Murine Biliary Atresia

et al. 2018

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Biliary atresia (BA) is a neonatal T cell-mediated, inflammatory, sclerosing cholangiopathy. In the rhesus rotavirus (RRV)-induced neonatal mouse model of BA (murine BA), mice lacking B cells do not develop BA, and the lack of B cells is associated with loss of T-cell and macrophage activation. The aim of this study was to determine the mechanism of B cell-mediated immune activation (antigen presentation versus cytokine production) in murine BA. Normal neonatal B cells in the liver are predominantly at pro-B and pre-B cellular development. However, BA mice exhibit a significant increase in the number and activation status of mature liver B cells. Adoptively transferred B cells into RRV-infected, B cell-deficient mice were able to reinstate T-cell and macrophage infiltration and biliary injury. Nonetheless, neonatal liver B cells were incompetent at antigen presentation to T cells. Moreover, 3-83 immunoglobulin transgenic mice, in which B cells only present an irrelevant antigen, developed BA, indicating a B-cell antigen-independent mechanism. B cells from BA mice produced a variety of innate and adaptive immune cytokines associated with immune activation. In vitro trans-well studies revealed that BA B cells secreted cytokines that activated T cells based on increased expression of T-cell activation marker cluster of differentiation 69. Conclusion: Neonatal liver B cells are highly activated in murine BA and contribute to immune activation through production of numerous cytokines involved in innate and adaptive immunity; this work provides increased knowledge on the capacity of neonatal B cells to contribute to an inflammatory disease through cytokine-mediated mechanisms, and future studies should focus on targeting B cells as a therapeutic intervention in human BA.

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