☆ 4.7 Review

The emerging roles and therapeutic potential of B cells in sepsis

FRONTIERS IN PHARMACOLOGY (2022)

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Review Physiology

Sepsis-Induced Immunosuppression

Lisa K. Torres et al.

Summary: Sepsis is expected to have a significant impact on public health and cost as its prevalence increases. Factors contributing to the increased prevalence include aging population, immunomodulatory treatments, and immune-suppressing therapies. Sepsis-induced immunosuppression has been recognized as a predisposing factor in susceptibility to secondary infections and mortality. This review discusses the mechanisms of sepsis-induced immunosuppression, biomarkers for impaired immunity, immune-enhancing strategies, and ongoing therapeutics in sepsis patients. Furthermore, future challenges and the need for personalized immunotherapy are highlighted.

ANNUAL REVIEW OF PHYSIOLOGY (2022)

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Marginal Zone B-Cell Populations and Their Regulatory Potential in the Context of HIV and Other Chronic Inflammatory Conditions

Kim Doyon-Laliberte et al.

Summary: Inflammation caused by Human Immunodeficiency Virus (HIV) can lead to dysregulation of B-cell populations, increasing the risk of chronic inflammation and autoimmune diseases. Restoring B-cell function in the context of chronic inflammation involving excess BAFF could be beneficial.

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Article Respiratory System

Plasma cell but not CD20-mediated B cell depletion protects from bleomycin-induced lung fibrosis

Cecilia M. Prêle et al.

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Alteration of macrophage immune phenotype in a murine sepsis model is associated with susceptibility to infection

Chau Tran Bao Vu et al.

Summary: This study evaluated the kinetic changes in immune cells in murine sepsis and found that macrophage activation and exhaustion may play a significant role in susceptibility to fungal infection and outcomes.

ASIAN PACIFIC JOURNAL OF ALLERGY AND IMMUNOLOGY (2022)

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Article Cell Biology

Artemisinin attenuates IgM xenoantibody production via inhibition of T cell-independent marginal zone B cell proliferation

Lihua Liu et al.

Summary: Artemisinin suppresses B cell immune responses by inhibiting splenic marginal zone (MZ) B cells and other B cells, leading to reduced T cell-independent xenogeneic IgM antibody production and impairment of IL-10 production, representing a new mechanism of ART-induced immunosuppression.

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Low immunoglobulin G level is associated with poor outcomes in patients with sepsis and septic shock

Masayuki Akatsuka et al.

Summary: Low IgG levels are associated with higher 28-day mortality in critically ill patients; survivors have significantly higher serum IgG levels compared to non-survivors; patients with low IgG levels have significantly higher mortality rates compared to those with normal levels.

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Skewed CD39/CD73/adenosine pathway contributes to B-cell hyperactivation and disease progression in patients with chronic hepatitis B

Shuang-Nan Zhou et al.

Summary: The study revealed that skewed CD39 and CD73 expression on B-cells in chronic hepatitis B patients was associated with high viral burden, liver inflammation, and antiviral efficacy, and the skewed CD39/CD73/adenosine pathway contributed to B-cell hyperactivation.

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B cell depletion therapies in autoimmune disease: advances and mechanistic insights

Dennis S. W. Lee et al.

Summary: B cells have been found to actively participate in autoimmune diseases, leading to the clinical success of B cell depletion therapies like those targeting CD20, CD19, and BAFF. Despite limited impact on antibody levels and plasma cells in controlling the disease, research on B cells is constantly evolving and developing.

NATURE REVIEWS DRUG DISCOVERY (2021)

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The immunology of sepsis

Tom van der Poll et al.

Summary: Sepsis is a life-threatening condition caused by infection-induced organ dysfunction, characterized by unbalanced hyperinflammation and immune suppression. Current research aims to stratify sepsis patients into more similar subgroups to better identify those who are likely to benefit from specific immune interventions.

IMMUNITY (2021)

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Review Immunology

The Role of Siglec-G on Immune Cells in Sepsis

William Royster et al.

Summary: Siglec-G plays an important immunoregulatory role in B-1a cells and myeloid cells, contributing to the potential therapeutic approach in treating sepsis. A clear understanding of Siglec-G is crucial in developing novel therapeutics for sepsis.

FRONTIERS IN IMMUNOLOGY (2021)

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Review Immunology

Immune Deregulation in Sepsis and Septic Shock: Reversing Immune Paralysis by Targeting PD-1/PD-L1 Pathway

Yuki Nakamori et al.

Summary: Sepsis is a disease characterized by a dysregulated host response to infection, with both inflammation and immune suppression occurring, and no specific treatment has been validated. The challenge lies in the complexity and heterogeneity of sepsis, requiring the selection of homogenous sepsis subgroups for testing experimental therapies. Artificial intelligence may help in identifying the most suitable subgroup for specific pathway inhibitors.

FRONTIERS IN IMMUNOLOGY (2021)

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Higher levels of IgA and IgG at sepsis onset are associated with higher mortality: results from the Albumin Italian Outcome Sepsis (ALBIOS) trial

Laura Alagna et al.

Summary: The study found that high levels of IgA and IgG on the first day of diagnosis in patients with severe sepsis or septic shock were associated with decreased 90-day survival, while no association was found between IgM levels and survival.

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The Dynamics of B Cell Aging in Health and Disease

Jill de Mol et al.

Summary: Aging is a significant risk factor for inflammatory diseases, where B cells play a crucial role. Different B cell subsets are involved in infections and autoimmune diseases. With age-related changes in B cell development and function, the impact on chronic inflammatory diseases can be substantial.

FRONTIERS IN IMMUNOLOGY (2021)

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T Cell/B Cell Interactions in the Establishment of Protective Immunity

Julia Ritzau-Jost et al.

Summary: This review discusses the optimization of Tfh cell generation and their interaction with B cells for therapeutic purposes. It also summarizes different T cell subsets, including Tph cells, and highlights the importance of T cell/B cell interaction in non-lymphoid tissues for the generation of protective antibodies.

VACCINES (2021)

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A Comparison Between 1 Day versus 7 Days of Sepsis in Mice with the Experiments on LPS-Activated Macrophages Support the Use of Intravenous Immunoglobulin for Sepsis Attenuation

Jiradej Makjaroen et al.

Summary: This study explored the immune adaptation and dysregulation in sepsis survivors and moribund mice after CLP surgery, as well as in vitro macrophage experiments. The results showed that survivors exhibited normalized parameters, enhanced adaptive immunity, and reduced liver injury, endotoxemia, and gut leakage. Soluble heat aggregated immunoglobulin (sHA-Ig) reduced inflammation in LPS-activated macrophages, while intravenous immunoglobulin (IVIG) attenuated sepsis severity and improved survival in CLP mice. These findings suggest that immunoglobulins may play a role in modulating immune responses in sepsis and IVIG could be beneficial under certain conditions.

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Cytokine-skewed Tfh cells: functional consequences for B cell help

Adesola C. Olatunde et al.

Summary: Tfh cells are crucial for providing help for B cells in germinal centers, contributing to effective and long-lasting humoral immune responses. The cytokine-skewed differentiation and functions of Tfh cells play a significant role in modulating disease progression and humoral immune responses.

TRENDS IN IMMUNOLOGY (2021)

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A primitive type of renin-expressing lymphocyte protects the organism against infections

Brian C. Belyea et al.

Summary: Renin hormone plays a crucial role in regulating blood pressure and fluid-electrolyte balance, synthesized and released by juxtaglomerular (JG) cells. Additionally, a unique type of renin-expressing B-1 lymphocyte has been discovered outside of the kidney, potentially playing a role in defending the organism against infections.

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Immunosuppressive Mechanisms of Regulatory B Cells

Diego Catalan et al.

Summary: Regulatory B cells play a crucial role in maintaining immune tolerance and preventing exacerbated inflammatory responses. In addition to IL-10, other molecules such as IL-35, TGF-beta, and cell surface proteins like CD1d and PD-L1 are utilized by Bregs to regulate immune responses.

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Marginal Zone B Cells Assist With Neutrophil Accumulation to Fight Against Systemic Staphylococcus aureus Infection

Li-Wen Lo et al.

Summary: Recent studies have shown that MZ B cells play a crucial role in regulating neutrophil migration in the spleen during systemic S. aureus infection, contributing to pathogen clearance. The upregulation of IL-6 and CXCL1/CXCL2 in MZ B cells post-infection promotes neutrophil recruitment. Interaction between neutrophils and MZ B cells is pivotal for IgM-secreting cell differentiation and overall immune response.

FRONTIERS IN IMMUNOLOGY (2021)

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Summary: Sepsis is a life-threatening global disease burden, with current treatment mainly relying on basic measures and limited effectiveness of adjuvant therapy. Therefore, a deeper understanding of sepsis immunopathophysiology is needed to explore more promising therapeutic approaches.

FRONTIERS IN MEDICINE (2021)

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Sepsis expands a CD39+ plasmablast population that promotes immunosuppression via adenosine-mediated inhibition of macrophage antimicrobial activity

Daniele Carvalho Nascimento et al.

Summary: Adenosine signaling through CD39(hi) plasmablasts plays a critical role in sepsis-induced immunosuppression, leading to increased risk of secondary infections. CD39(hi) plasmablasts enhance adenosine accumulation, impairing macrophage bactericidal activity and promoting interleukin-10 production, contributing to immune suppression post-sepsis.

IMMUNITY (2021)

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Crosstalk between B cells and neutrophils in rheumatoid arthritis

Utsa Karmakar et al.

Summary: RA is a chronic autoimmune disease affecting synovial joints, driven by a vicious circle between B cells and neutrophils. ACPA and other autoantibodies play a key role in promoting disease progression.

IMMUNOLOGY (2021)

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Article Immunology

Marginating transitional B cells modulate neutrophils in the lung during inflammation and pneumonia

John Podstawka et al.

Summary: This study identified multiple IgM(+) B cell subsets in the lung circulation, with transitional type B and T2B cells playing a crucial role in regulating neutrophil inflammation responses.

JOURNAL OF EXPERIMENTAL MEDICINE (2021)

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Article Immunology

Imbalance between inflammatory and regulatory cord blood B cells following pre-term birth

Mandy Busse et al.

Summary: The study found that preterm birth is associated with an imbalance in cord blood cell immune responses, with B cells playing a key role, which may contribute to increased mortality and morbidity in preterm infants.

JOURNAL OF REPRODUCTIVE IMMUNOLOGY (2021)

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Article Biochemistry & Molecular Biology

Extracellular CIRP decreases Siglec-G expression on B-1a cells skewing them towards a pro-inflammatory phenotype in sepsis

William Royster et al.

Summary: eCIRP reduces the population of PerC B-1a cells and promotes a pro-inflammatory phenotype by downregulating Siglec-G expression. Targeting eCIRP may help retain Siglec-G-expressing B-1a cells in the PerC and preserve their anti-inflammatory function during sepsis.

MOLECULAR MEDICINE (2021)

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Article Immunology

Neutrophil Extracellular Traps Activate Proinflammatory Functions of Human Neutrophils

Daniel Doemer et al.

Summary: This study provides a comprehensive analysis of the effects of NETs on human primary neutrophils in vitro. The results demonstrate that NETs can activate various neutrophil functions, including ROS production, phagocytosis and killing of microbial pathogens. Additionally, NETs induce the secretion of inflammatory cytokines, further supporting their role in amplifying inflammatory events.

FRONTIERS IN IMMUNOLOGY (2021)

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Follicular dendritic cell dysfunction contributes to impaired antigen-specific humoral responses in sepsis-surviving mice

Minakshi Rana et al.

Summary: Sepsis survivors demonstrate impaired humoral response to antigen challenge, which is attributed to dysfunction in follicular dendritic cells (FDCs) and germinal center (GC) B cells.

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Article Critical Care Medicine

POPULATION-SPECIFIC METABOLIC ALTERATIONS IN PROFESSIONAL ANTIGEN-PRESENTING CELLS CONTRIBUTE TO SEPSIS-ASSOCIATED IMMUNOSUPPRESSION

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Dendritic cells license regulatory B cells to produce IL-10 and mediate suppression of antigen-specific CD8 T cells

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The increased marginal zone B cells attenuates early inflammatory responses during sepsis in Gpr174 deficient mice

Ming Zhu et al.

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Impaired B-Cell Maturation Contributes to Reduced B Cell Numbers and Poor Prognosis in Sepsis

Shaoxia Duan et al.

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B lymphocytopenia and Bregs in a not-to-die murine sepsis model

Kensuke Umakoshi et al.

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Global, regional, and national sepsis incidence and mortality, 1990-2017: analysis for the Global Burden of Disease Study

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Georg F. Weber et al.

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Targeting Siglecs with a sialic acid-decorated nanoparticle abrogates inflammation

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SCIENCE TRANSLATIONAL MEDICINE (2015)

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Review Immunology

The generation of antibody-secreting plasma cells

Stephen L. Nutt et al.

NATURE REVIEWS IMMUNOLOGY (2015)

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Immunoglobulins IgG1, IgM and IgA: a synergistic team influencing survival in sepsis

J. F. Bermejo-Martin et al.

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IL-35-producing B cells are critical regulators of immunity during autoimmune and infectious diseases

Ping Shen et al.

NATURE (2014)

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Interleukin-35 induces regulatory B cells that suppress autoimmune disease

Ren-Xi Wang et al.

NATURE MEDICINE (2014)

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Early alterations of B cells in patients with septic shock

Jorge Monserrat et al.

CRITICAL CARE (2013)

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Article Critical Care Medicine

Kinetics of circulating immunoglobulin M in sepsis: relationship with final outcome

Evangelos J. Giamarellos-Bourboulis et al.

CRITICAL CARE (2013)

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Article Immunology

Sepsis leads to a reduced antigen-specific primary antibody response

Arno Mohr et al.

EUROPEAN JOURNAL OF IMMUNOLOGY (2012)

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Editorial Material Immunology

Newly discovered innate response activator B cells: crucial responders against microbial sepsis

Clinton S. Robbins et al.

EXPERT REVIEW OF CLINICAL IMMUNOLOGY (2012)

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Review Immunology

B-1 B Cell Development in the Fetus and Adult

Encarnacion Montecino-Rodriguez et al.

IMMUNITY (2012)

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Article Cell Biology

Pre-inflammatory Mediators and Lymphocyte Subpopulations in Preterm Neonates with Sepsis

Efthalia Hotoura et al.

INFLAMMATION (2012)

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Article Immunology

Marginal Zone B Cell Is a Major Source of Il-10 in Listeria monocytogenes Susceptibility

Chen-Cheng Lee et al.

JOURNAL OF IMMUNOLOGY (2012)

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Article Multidisciplinary Sciences

Innate Response Activator B Cells Protect Against Microbial Sepsis

Philipp J. Rauch et al.

SCIENCE (2012)

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Article Immunology

B-1 cells temper endotoxemic inflammatory responses

Denise Frediani Barbeiro et al.

IMMUNOBIOLOGY (2011)

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Article Medicine, General & Internal

Immunosuppression in Patients Who Die of Sepsis and Multiple Organ Failure

Jonathan S. Boomer et al.

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION (2011)

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Article Immunology

B cells enhance early innate immune responses during bacterial sepsis

Kindra M. Kelly-Scumpia et al.

JOURNAL OF EXPERIMENTAL MEDICINE (2011)

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Article Biotechnology & Applied Microbiology

Amelioration of sepsis by inhibiting sialidase-mediated disruption of the CD24-SiglecG interaction

Guo-Yun Chen et al.

NATURE BIOTECHNOLOGY (2011)

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Article Immunology

Tracking Changes of Lymphocyte Subsets and Pre-inflammatory Mediators in Full-term Neonates with Suspected or Documented Infection

E. Hotoura et al.

SCANDINAVIAN JOURNAL OF IMMUNOLOGY (2011)

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Article Critical Care Medicine

Early natural killer cell counts in blood predict mortality in severe sepsis

David Andaluz-Ojeda et al.

CRITICAL CARE (2011)

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EARLY ASSESSMENT OF LEUKOCYTE ALTERATIONS AT DIAGNOSIS OF SEPTIC SHOCK

Fabienne Venet et al.

SHOCK (2010)

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Article Critical Care Medicine

Early alterations of the innate and adaptive immune statuses in sepsis according to the type of underlying infection

Charalambos Gogos et al.

CRITICAL CARE (2010)

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Article Immunology

Role of Marginal Zone B Lymphocytes in Invariant NKT Cell Activation

Emilie Bialecki et al.

JOURNAL OF IMMUNOLOGY (2009)

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PD-1 expression by macrophages plays a pathologic role in altering microbial clearance and the innate inflammatory response to sepsis

Xin Huang et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2009)

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Article Critical Care Medicine

Immunoglobulin G treatment of postcardiac surgery patients with score-identified severe systemic inflammatory response syndrome - The ESSICS study

Karl Werdan et al.

CRITICAL CARE MEDICINE (2008)

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Review Immunology

Peripheral B cell subsets

David Allman et al.

CURRENT OPINION IN IMMUNOLOGY (2008)

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Article Critical Care Medicine

High-dose intravenous immunoglobulin G improves systemic inflammation in a rat model of CLP-induced sepsis

Satoshi Hagiwara et al.

INTENSIVE CARE MEDICINE (2008)

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BAFF and LPS cooperate to induce B cells to become susceptible to CD95/Fas-mediated cell death

Eva V. Acosta-Rodriguez et al.

EUROPEAN JOURNAL OF IMMUNOLOGY (2007)

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Evidence that marginal zone B cells possess an enhanced secretory apparatus and exhibit superior secretory activity

Kathryn E. Gunn et al.

JOURNAL OF IMMUNOLOGY (2006)

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Accelerated lymphocyte death in sepsis occurs by both the death receptor and mitochondrial pathways

RS Hotchkiss et al.

JOURNAL OF IMMUNOLOGY (2005)

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Effects of repeated social stress on leukocyte distribution in bone marrow, peripheral blood and spleen

H Engler et al.

JOURNAL OF NEUROIMMUNOLOGY (2004)

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Article Infectious Diseases

Lymphocyte subset numbers depend on the bacterial origin of sepsis

M Holub et al.

CLINICAL MICROBIOLOGY AND INFECTION (2003)

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Article Immunology

Sepsis-induced apoptosis causes progressive profound depletion of B and CD4+ T lymphocytes in humans

RS Hotchkiss et al.

JOURNAL OF IMMUNOLOGY (2001)

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Increased apoptosis in lamina propria B cells during polymicrobial sepsis is FasL but not endotoxin mediated

CS Chung et al.

AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY (2001)

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Absence of marginal zone B cells in Pyk-2-deficient mice defines their role in the humoral response

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NATURE IMMUNOLOGY (2000)

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