Germinal Center B-cells.

23:45 EDT 4th September 2015 | BioPortfolio

Summary of "Germinal Center B-cells."

Within the B-cell follicle of secondary lymphoid organs, germinal center (GC) reactions produce high affinity antibody-secreting plasma cells (PCs) and memory B-cells necessary for the host's defense against invading pathogens. This process of GC formation is reliant on the activation of antigen-specific B-cells by T-cells capable of recognizing epitopes of the same antigenic complex. The unique architecture of secondary lymphoid organs facilitates these initial GC events through the placement of large clonally-diverse B-cell follicles near equally diverse T-cell zones. Antigen-activated B-cells that receive proper differentiation signals at the T-cell border of the B-cell follicle initiate an early GC B-cell transcriptional profile and migrate to follicular dendritic cell (FDC) networks within the B-cell follicle to seed the GC reaction. Peripheral to FDCs, GC B-cells rapidly divide in dark zones of the GC, and undergo somatic hypermutation of their immunoglobulin (Ig) variable domain. Newly formed GC B-cell clones then migrate into the GC light zone where they compete for antigen and secondary signals presented by FDCs and a specialized subset of CD4(+) T-cells known as T-follicular helper cells. Survival, proliferative and differentiation signals delivered by mature FDCs and T(FH) cells initiate transcriptional programs that determine if GC B-cells become memory B-cells or terminally differentiated PCs. To prevent oncogenic transformation and/or the escape of autoreactive clones, there are several regulatory mechanisms that restrict GC B-cell proliferation and survival. Here we will detail the recent advances in GC B-cell biology that relate to their generation and fate-determination as well as their pathogenic potential.

Affiliation

Department of Medicine, Section of Rheumatology and Gwen Knapp Center for Lupus and Immunology Research, The University of Chicago , Chicago, Illinois 60637 , USA.

Journal Details

This article was published in the following journal.

Name: Autoimmunity
ISSN: 1607-842X
Pages:

Links

PubMed Articles [18291 Associated PubMed Articles listed on BioPortfolio]

Treg Cells and CTLA-4: The Ball and Chain of the Germinal Center Response.

The mechanism by which regulatory T cells control the germinal center response is unknown. In this issue of Immunity, Wing et al. (2014) and Sage et al. (2014) demonstrate that CTLA-4 is a critical...

Unexpected functions of nuclear factor-κB during germinal center B-cell development: implications for lymphomagenesis.

B-cell tumors originating from the transformation of germinal center B cells frequently harbor genetic mutations, leading to constitutive activation of the nuclear factor-κB (NF-κB) signaling pathwa...

Germinal center quality control: death by fas.

Fas is a cell surface death receptor critical for immune regulation. In this issue of Immunity, Butt et al. (2015) show that Fas eliminates B cells that have become uncoupled from positive and negati...

Deletion of WASp and N-WASp in B cells cripples the germinal center response and results in production of IgM autoantibodies.

Humoral immunodeficiency caused by mutations in the Wiskott-Aldrich syndrome protein (WASp) is associated with failure to respond to common pathogens and high frequency of autoimmunity. Here we addres...

TLR7 Influences Germinal Center Selection in Murine SLE.

TLR7 enhances germinal center maturation and migration of B cells to the dark zone where proliferation and somatic hypermutation occur. Our goal was to determine how Tlr7 dose influences selection of ...

Clinical Trials [4984 Associated Clinical Trials listed on BioPortfolio]

Study to Assess the Effectiveness of RCHOP With or Without VELCADE in Previously Untreated Non-Germinal Center B-Cell-like Diffuse Large B-Cell Lymphoma Patients

This is a randomized, open-label, multi-center, phase 2 study of RCHOP with or without VELCADE in adult patients with previously untreated non-(Germinal B-Cell-like) GCB Diffuse Large B-ce...

A Study of the Bruton's Tyrosine Kinase Inhibitor, PCI-32765 (Ibrutinib), in Combination With Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone in Patients With Newly Diagnosed Non-Germinal Center B-Cell Subtype of Diffuse Large B-Cell

The purpose of this study is to evaluate if ibrutinib administered in combination with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) improves the clinical ...

Phase II Study of "VIPER" Chemotherapy in Rel/Ref DLBCL

Objectives The primary objective of this study is to: • determine the complete and partial response rates and the toxicity profile of bortezomib (VELCADE, formerly PS-341) when a...

Pharmacogenomic Study to Predict Neurotoxicity of Oxaliplatin

In order to explore genetic factors that may determine the neurotoxicity of oxaliplatin-based chemotherapy, germinal gene polymorphisms will be analyzed.

Indomethacin Germinal Matrix Hemorrhage/Intraventricular Hemorrhage (GMH/IVH) Prevention Trial

The purpose of this multicenter trial is to determine if indomethacin prevents bleeding in the brain of very low birth weight preterm infants.

Medical and Biotech [MESH] Definitions

The activated center of a lymphoid follicle in secondary lymphoid tissue where B-LYMPHOCYTES are stimulated by antigens and helper T cells (T-LYMPHOCYTES, HELPER-INDUCER) are stimulated to generate memory cells.

Malignant lymphoma in which the lymphomatous cells are clustered into identifiable nodules within the LYMPH NODES. The nodules resemble to some extent the GERMINAL CENTER of lymph node follicles and most likely represent neoplastic proliferation of lymph node-derived follicular center B-LYMPHOCYTES.

A member of the tumor necrosis factor receptor superfamily with specificity for CD40 LIGAND. It is found on mature B-LYMPHOCYTES and some EPITHELIAL CELLS, lymphoid DENDRITIC CELLS. Evidence suggests that CD40-dependent activation of B-cells is important for generation of memory B-cells within the germinal centers. Mutations of the gene for CD40 antigen result in HYPER-IGM IMMUNODEFICIENCY SYNDROME, TYPE 3. Signaling of the receptor occurs through its association with TNF RECEPTOR-ASSOCIATED FACTORS.

A center in the PUBLIC HEALTH SERVICE which coordinates and administers a program of research, demonstrations, and evaluations of medical technologies and assessments of health care technology.

Neurons of the innermost layer of the retina, the internal plexiform layer. They are of variable sizes and shapes, and their axons project via the OPTIC NERVE to the brain. A small subset of these cells act as photoreceptors with projections to the SUPRACHIASMATIC NUCLEUS, the center for regulating CIRCADIAN RHYTHM.


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