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28. Editorial: Integrative Computational Systems Biology Approaches in Immunology and Medicine

Author

Kaderali, Lars, Theis, Fabian, Ganusov, Vitaly V., Ciupe, Mihaela Stanca, Mehr, Ramit, Ribeiro, Ruy M., Hernandez-Vargas, Esteban A., Kaderali, Lars, Theis, Fabian, Ganusov, Vitaly V., Ciupe, Mihaela Stanca, Mehr, Ramit, Ribeiro, Ruy M., and Hernandez-Vargas, Esteban A.

Abstract

New technologies provide the ability to generate massive amounts of immunological data in health and disease. However, this “Big data” trend is becoming more challenging and unfeasible by the steep increase in the number of different pieces of information and the complexity of large datasets. Thus, systematic and tractable approaches that integrate a variety of biological and medical research data at multiple scales into mathematical, statistical, and computational models are crucial to harness knowledge and to develop new therapies...

Published
2019
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29. Editorial: Integrative Computational Systems Biology Approaches in Immunology and Medicine

Author

Mathematics, Kaderali, Lars, Theis, Fabian, Ganusov, Vitaly V., Ciupe, Stanca M., Mehr, Ramit, Ribeiro, Ruy M., Hernandez-Vargas, Esteban A., Mathematics, Kaderali, Lars, Theis, Fabian, Ganusov, Vitaly V., Ciupe, Stanca M., Mehr, Ramit, Ribeiro, Ruy M., and Hernandez-Vargas, Esteban A.

Abstract

New technologies provide the ability to generate massive amounts of immunological data in health and disease. However, this “Big data” trend is becoming more challenging and unfeasible by the steep increase in the number of different pieces of information and the complexity of large datasets. Thus, systematic and tractable approaches that integrate a variety of biological and medical research data at multiple scales into mathematical, statistical, and computational models are crucial to harness knowledge and to develop new therapies...

Published
2019

30. Editorial : integrative computational systems biology approaches in immunology and medicine

Author

Collin, Mattias, Kaderali, Lars, Theis, Fabian J., Ganusov, Vitaly V., Ciupe, Stanca M., Mehr, Ramit, Ribeiro, Ruy M., Hernandez-Vargas, Esteban Abelardo, Collin, Mattias, Kaderali, Lars, Theis, Fabian J., Ganusov, Vitaly V., Ciupe, Stanca M., Mehr, Ramit, Ribeiro, Ruy M., and Hernandez-Vargas, Esteban Abelardo

Abstract

Editorial on the Research Topic "Integrative Computational Systems Biology Approaches in Immunology and Medicine"

Published
2019

35. Depletion of B cells rejuvenates the peripheral B‐cell compartment but is insufficient to restore immune competence in aging

Author

Avivi, Irit, primary, Zisman‐Rozen, Simona, additional, Naor, Shulamit, additional, Dai, Isabelle, additional, Benhamou, David, additional, Shahaf, Gitit, additional, Tabibian‐Keissar, Hilla, additional, Rosenthal, Noemie, additional, Rakovsky, Aviya, additional, Hanna, Ammuri, additional, Shechter, Arik, additional, Peled, Eli, additional, Benyamini, Noam, additional, Dmitrukha, Ekaterina, additional, Barshack, Iris, additional, Mehr, Ramit, additional, and Melamed, Doron, additional

Published
2019
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38. Role of the thymus in pediatric HIV-1 infection

Author

Kirschner, Denise E., Mehr, Ramit, and Perelson, Alan S.

Subjects
HIV infection in children -- Development and progression, Thymus -- Physiological aspects, HIV (Viruses), Health
Abstract

Infection within the thymus gland may act as a viral reservoir in HIV infection and contribute to the rapid progression to AIDS in pediatric patients. Cells within the thymus gland differentiate into CD4+ T-cells, which are critical for immune function and decrease in number as HIV infection progresses to AIDS. Researchers developed a mathematical formula to describe HIV infection in the thymus gland, and determined that viral infection of thymus cells can occur at a higher rate than infection of cells in the bloodstream and other parts of the body.

Published
1998

40. Blind T-cell homeostasis and the CD4/CD8 ratio in the thymus and peripheral blood

Author

Mehr, Ramit and Perelson, Alan S.

Subjects
HIV infection -- Models, T cells -- Measurement, Health
Abstract

A mathematical model has confirmed the blind T-cell homeostasis theory. This theory states that only the total number of T cells is regulated, not the number of T cells in each subset. The theory was based on an experiment in which mice were treated with a monoclonal antibody against CD4 T cells, which caused the number of these cells to drop. However, the number of CD8 T cells rose so that the total number of T cells did not change. The mathematical model confirmed the theory only when the equations supported the regulation of the total number of T cells.

Published
1997

41. Ibrutinib, Bendamustine, Rituximab Combination for Relapsed and Refractory Aggressive B Cell Lymphoma — Interim Analysis of Phase II Clinical Trial

Author

Kedmi, Meirav, primary, Ribakovsy, Elena, additional, Benjamini, Ohad, additional, Schiby, Ginette, additional, Barshack, Iris, additional, Raskin, Stephen P, additional, Eshet, Yael, additional, Mehr, Ramit, additional, Bitansky, Guy, additional, Nagler, Arnon, additional, and Avigdor, Abraham, additional

Published
2018
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42. Murine peripheral NK-cell populations originate from site-specific immature NK cells more than from BM-derived NK cells

Author

Pinhas, Nissim, Sternberg-Simon, Michal, Chiossone, Laura, Shahaf, Gitit, Walzer, Thierry, Vivier, Eric, Mehr, Ramit, Centre d'Immunologie de Marseille - Luminy (CIML), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), and Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[SDV.IMM]Life Sciences [q-bio]/Immunology
Abstract

International audience; Murine NK cells can be divided by the expression of two cell surface markers, CD27 and Mac-1 (a.k.a. CD11b), into four separate subsets. These subsets suggest a linear development model: CD27(-) Mac-1(-) -> CD27(+) Mac-1(-) -> CD27(+) Mac-1(+) -> CD27(-) Mac-1(+). Here, we used a combination of BrdU labeling experiments and mathematical modeling to gain insights regarding NK-cell development in mouse bone marrow (BM), spleen and liver. The modeling results that best fit the experimental data show that the majority of NK cells already express CD27 upon entering the NK-cell developmental pathway. Additionally, only a small fraction of NK cells exit the BM to other sites, suggesting that peripheral NK-cell populations originate from site-specific immature NK cells more than from BM-derived mature NK cells.

Published
2016

44. The VH repertoire and clonal diversification of B cells in inflammatory myopathies

Author

McIntyre, Donna, Zuckerman, Neta S., Field, Max, Mehr, Ramit, and Stott, David I.

Abstract

The contribution of antigen-driven B-cell adaptive immune responses within the inflamed muscle of inflammatory myopathies (IMs) is largely unknown. In this study, we investigated the immunoglobulin VH gene repertoire, somatic hypermutation, clonal diversification, and selection of infiltrating B cells in muscle biopsies from IM patients (dermatomyositis and polymyositis), to determine whether B cells and/or plasma cells contribute to the associated pathologies of these diseases. The data reveal that Ig VH gene repertoires of muscle-infiltrating B cells deviate from the normal VH gene repertoire in individual patients, and differ between different types of IMs. Analysis of somatic mutations revealed clonal diversification of muscle-infiltrating B cells and evidence for a chronic B-cell response within the inflamed muscle. We conclude that muscle-infiltrating B cells undergo selection, somatic hypermutation and clonal diversification in situ during antigen-driven immune responses in patients with IMs, providing insight into the contribution of B cells to the pathological mechanisms of these disorders.

Published
2014

46. Long-lived antigen-induced IgM plasma cells demonstrate somatic mutations and contribute to long-term protection

Author

Bohannon, Caitlin, primary, Powers, Ryan, additional, Satyabhama, Lakshmipriyadarshini, additional, Cui, Ang, additional, Tipton, Christopher, additional, Michaeli, Miri, additional, Skountzou, Ioanna, additional, Mittler, Robert S., additional, Kleinstein, Steven H., additional, Mehr, Ramit, additional, Lee, Frances Eun-Yun, additional, Sanz, Ignacio, additional, and Jacob, Joshy, additional

Published
2016
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48. Aging affects B-cell antigen receptor repertoire diversity in primary and secondary lymphoid tissues

Author

Tabibian-Keissar, Hilla, primary, Hazanov, Lena, additional, Schiby, Ginette, additional, Rosenthal, Noemie, additional, Rakovsky, Aviya, additional, Michaeli, Miri, additional, Shahaf, Gitit Lavy, additional, Pickman, Yishai, additional, Rosenblatt, Kinneret, additional, Melamed, Doron, additional, Dunn-Walters, Deborah, additional, Mehr, Ramit, additional, and Barshack, Iris, additional

Published
2015
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49. Lyn deficiency affects B cell maturation as well as survival

Author

Shahaf, Gitit, Gross, Andrew J., Sternberg-Simon, Michal, Kaplan, Deborah, DeFranco, Anthony L., and Mehr, Ramit

Subjects
Mice, Knockout, Cell Survival, Receptors, IgE, Precursor Cells, B-Lymphoid, B-Lymphocyte Subsets, Receptors, Antigen, B-Cell, Cell Differentiation, Cell Separation, Models, Theoretical, Flow Cytometry, Article, Mice, Inbred C57BL, Mice, src-Family Kinases, Immunoglobulin M, hemic and lymphatic diseases, Animals, Cells, Cultured, Spleen, Signal Transduction
Abstract

Lyn, a Src-family protein tyrosine kinase expressed in B lymphocytes, contributes to initiation of BCR signaling and is also responsible for feedback inhibition of BCR signaling. Lyn-deficient mice have a decreased number of follicular B cells and also spontaneously develop a lupus-like autoimmunity. We used flow cytometric analysis, BrdU labeling, and our mathematical models of B cell population dynamics, to analyze how Lyn deficiency impacts B-cell maturation and survival. We found that Lyn-deficient transitional 1 (T1) cells develop normally, but T2 cells develop primarily from the T1 subset in the spleen and fail to also develop directly from bone marrow immature B cells. Lyn-deficient T2 cells either mature to the follicular B-cell type at a close to normal rate, or die in this compartment rather than access the T3 anergic subset. The ~40% of wild type follicular cells that were short-lived exited primarily by joining the T3 anergic subset, whereas the ~15% Lyn−/− follicular cells that were not long-lived had a high death rate and died in this compartment rather than entering the T3 subset. We hypothesize that exaggerated BCR signaling resulting from weak interactions with self-antigens is largely responsible for these alterations in Lyn-deficient B cells.

Published
2011

50. High Throughput Sequencing Analysis of the Immunoglobulin Heavy Chain Gene from Flow-Sorted B Cell Sub-Populations Define the Dynamics of Follicular Lymphoma Clonal Evolution

Author

Carlotti, Emanuela, primary, Wrench, David, additional, Rosignoli, Guglielmo, additional, Marzec, Jacek, additional, Sangaralingam, Ajanthah, additional, Hazanov, Lena, additional, Michaeli, Miri, additional, Hallam, Simon, additional, Chaplin, Tracy, additional, Iqbal, Sameena, additional, Calaminici, Maria, additional, Young, Bryan, additional, Mehr, Ramit, additional, Campbell, Peter, additional, Fitzgibbon, Jude, additional, and Gribben, John G., additional

Published
2015
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