4.8 Review

Compartments and Connections Within the Germinal Center

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Article Immunology

Exit from germinal center to become quiescent memory B cells depends on metabolic reprograming and provision of a survival signal

Takeshi Inoue et al.

Summary: This study found that GC-derived CD38(int)Bcl6(hi/int)Efnb1(center dot) cells with lower mTORC1 activity are more likely to become memory B cells, with higher levels of Bcl2 and BCR contributing to their survival and development. Weak T cell help and increased survival signals are key factors for GC B cells to adopt a memory B cell fate.

JOURNAL OF EXPERIMENTAL MEDICINE (2021)

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Eliciting B cell immunity against infectious diseases using nanovaccines

Ankur Singh

Summary: This article discusses the advantages and disadvantages of nanoscale vaccines against infectious diseases, highlighting their impact on immune responses and the challenges in production. Complex nanovaccine technologies are being studied to induce a strong immune response against difficult pathogens.

NATURE NANOTECHNOLOGY (2021)

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Permissive selection followed by affinity-based proliferation of GC light zone B cells dictates cell fate and ensures clonal breadth

Rinako Nakagawa et al.

Summary: Affinity maturation in germinal centers depends on efficient positive selection of B cells in the light zone. Different subpopulations of cMyc(+) GC B cells are identified and characterized, with higher-affinity cells diverging towards plasmablasts and lower-affinity cells towards memory B cell precursors. This dynamic process of positive selection leads to the generation of three distinct B cell fates, ensuring clonal diversity for broad protection.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2021)

Article Immunology

Regulation of Decay Accelerating Factor Primes Human Germinal Center B Cells for Phagocytosis

Andy Dernstedt et al.

Summary: The study found that B cells downregulate DAF upon engagement with BCR, and T cell-dependent stimuli preferentially activate DAF(lo) B cells. DAF(lo) B cells in GC are more susceptible to complement-dependent phagocytosis, while DAF(hi) GC B cells show increased expression of the plasma cell marker Blimp-1.

FRONTIERS IN IMMUNOLOGY (2021)

Article Hematology

OBF1 and Oct factors control the germinal center transcriptional program

Shuang Song et al.

Summary: The study demonstrates that OBF1, OCT2, and OCT1 play crucial roles in B-cell specificity and GC formation, as they extensively colocalize on the promoters or enhancers of genes involved in GC formation. They regulate each other and are essential for proliferation of lymphoma cell lines derived from GC, indicating OBF1 controls a key regulatory node in GC differentiation.
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Multiscale Modeling of Germinal Center Recapitulates the Temporal Transition From Memory B Cells to Plasma Cells Differentiation as Regulated by Antigen Affinity-Based Tfh Cell Help

Elena Merino Tejero et al.

Summary: Germinal centers play a crucial role in the adaptive immune system by generating memory B cells and plasma cells that produce high affinity antibodies for effective immune protection. Cell-fate decisions in germinal centers involve various factors, including antigen, B-cell receptor affinity, T follicular helper cells, and transcription factors. Molecular modulations of the CD40 signaling pathway can influence the production of germinal center output cells.

FRONTIERS IN IMMUNOLOGY (2021)

Article Immunology

Single-cell analysis of human B cell maturation predicts how antibody class switching shapes selection dynamics

Hamish W. King et al.

Summary: Our study provides a comprehensive roadmap of human B cell maturation by analyzing single-cell transcriptomics and antibody repertoires, revealing the heterogeneity of memory B cells with diverse functional and signaling states. We reconstruct gene expression dynamics during B cell activation, showing a pre-germinal center state prepared for class switch recombination, and dissect how antibody class-dependent gene expression in germinal center and memory B cells is linked with potential fate and function influence. Our analyses uncover the dynamic cellular states that shape human B cell-mediated immunity, emphasizing the potential role of antibody isotype during antibody-based selection.

SCIENCE IMMUNOLOGY (2021)

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Novel specialized cell state and spatial compartments within the germinal center

Domenick E. Kennedy et al.

NATURE IMMUNOLOGY (2020)

Article Immunology

Single-cell analysis of germinal-center B cells informs on lymphoma cell of origin and outcome

Antony B. Holmes et al.

JOURNAL OF EXPERIMENTAL MEDICINE (2020)

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Antibody Affinity Shapes the Choice between Memory and Germinal Center B Cell Fates

Charlotte Viant et al.

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B cell memory: building two walls of protection against pathogens

Munir Akkaya et al.

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The cis-Regulatory Atlas of the Mouse Immune System

Hideyuki Yoshida et al.

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Germinal center-derived lymphomas: The darkest side of humoral immunity

Coraline Mlynarczyk et al.

IMMUNOLOGICAL REVIEWS (2019)

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B Cell Responses: Cell Interaction Dynamics and Decisions

Jason G. Cyster et al.

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Class-Switch Recombination Occurs Infrequently in Germinal Centers

Jonathan A. Roco et al.

IMMUNITY (2019)

Review Immunology

Remembrance of Things Past: Long-Term B Cell Memory After Infection and Vaccination

Anna-Karin E. Palm et al.

FRONTIERS IN IMMUNOLOGY (2019)

Review Immunology

Self-Reactive B Cells in the Germinal Center Reaction

Robert Brink et al.

ANNUAL REVIEW OF IMMUNOLOGY, VOL 36 (2018)

Article Immunology

The cell cycle restricts activation-induced cytidine deaminase activity to early G1

Qiao Wang et al.

JOURNAL OF EXPERIMENTAL MEDICINE (2017)

Article Multidisciplinary Sciences

The microanatomic segregation of selection by apoptosis in the germinal center

Christian T. Mayer et al.

SCIENCE (2017)

Article Multidisciplinary Sciences

CTCF orchestrates the germinal centre transcriptional program and prevents premature plasma cell differentiation

Arantxa Perez-Garcia et al.

NATURE COMMUNICATIONS (2017)

Article Multidisciplinary Sciences

Environmental sensing by mature B cells is controlled by the transcription factors PU.1 and SpiB

Simon N. Willis et al.

NATURE COMMUNICATIONS (2017)

Review Biochemistry & Molecular Biology

Putting p53 in Context

Edward R. Kastenhuber et al.

Review Immunology

Deconstructing the germinal center, one cell at a time

Chad R. Dufaud et al.

CURRENT OPINION IN IMMUNOLOGY (2017)

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Phosphatidylserine is a global immunosuppressive signal in efferocytosis, infectious disease, and cancer

R. B. Birge et al.

CELL DEATH AND DIFFERENTIATION (2016)

Review Immunology

Germinal Center B Cell Dynamics

Luka Mesin et al.

IMMUNITY (2016)

Article Immunology

Regulated selection of germinal-center cells into the memory B cell compartment

Ryo Shinnakasu et al.

NATURE IMMUNOLOGY (2016)

Article Multidisciplinary Sciences

Regulation of normal B-cell differentiation and malignant B-cell survival by OCT2

Daniel J. Hodson et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2016)

Article Multidisciplinary Sciences

T cell help controls the speed of the cell cycle in germinal center B cells

Alexander D. Gitlin et al.

SCIENCE (2015)

Review Immunology

Dynamics of B cells in germinal centres

Nilushi S. De Silva et al.

NATURE REVIEWS IMMUNOLOGY (2015)

Article Immunology

The transcription factors IRF8 and PU.1 negatively regulate plasma cell differentiation

Sebastian Carotta et al.

JOURNAL OF EXPERIMENTAL MEDICINE (2014)

Article Multidisciplinary Sciences

Clonal selection in the germinal centre by regulated proliferation and hypermutation

Alexander D. Gitlin et al.

NATURE (2014)

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Control of cell cycle transcription during G1 and S phases

Cosetta Bertoli et al.

NATURE REVIEWS MOLECULAR CELL BIOLOGY (2013)

Review Immunology

Germinal Centers

Gabriel D. Victora et al.

ANNUAL REVIEW OF IMMUNOLOGY, VOL 30 (2012)

Article Immunology

BCL6 positively regulates AID and germinal center gene expression via repression of miR-155

Katia Basso et al.

JOURNAL OF EXPERIMENTAL MEDICINE (2012)

Article Cell Biology

A Theory of Germinal Center B Cell Selection, Division, and Exit

Michael Meyer-Hermann et al.

CELL REPORTS (2012)

Review Immunology

Immunoglobulin class-switch DNA recombination: induction, targeting and beyond

Zhenming Xu et al.

NATURE REVIEWS IMMUNOLOGY (2012)

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Mitotic catastrophe: a mechanism for avoiding genomic instability

Ilio Vitale et al.

NATURE REVIEWS MOLECULAR CELL BIOLOGY (2011)

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B cells within germinal centers migrate preferentially from dark to light zone

Joost B. Beltman et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2011)

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Control systems and decision making for antibody production

Christopher C. Goodnow et al.

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EBI2 mediates B cell segregation between the outer and centre follicle

Joao P. Pereira et al.

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Follicular dendritic cells control engulfment of apoptotic bodies by secreting Mfge8

Jan Kranich et al.

JOURNAL OF EXPERIMENTAL MEDICINE (2008)

Article Multidisciplinary Sciences

In vivo imaging of germinal centres reveals a dynamic open structure

Tanja A. Schwickert et al.

NATURE (2007)

Article Multidisciplinary Sciences

Imaging of germinal center selection events during affinity maturation

Christopher D. C. Allen et al.

SCIENCE (2007)

Article Immunology

High affinity germinal center B cells are actively selected into the plasma cell compartment

Tri Giang Phan et al.

JOURNAL OF EXPERIMENTAL MEDICINE (2006)

Article Immunology

Direct repression of prdm1 by Bcl-6 inhibits plasmacytic differentiation

C Tunyaplin et al.

JOURNAL OF IMMUNOLOGY (2004)

Article Multidisciplinary Sciences

Autoimmune disease and impaired uptake of apoptotic cells in MFG-E8-deficient mice

R Hanayama et al.

SCIENCE (2004)

Review Biochemistry & Molecular Biology

Mechanisms of chromosomal translocations in B cell lymphomas

R Küppers et al.

ONCOGENE (2001)