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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.
Department of Medicine, Section of Rheumatology and Gwen Knapp Center for Lupus and Immunology Research, The University of Chicago , Chicago, Illinois 60637 , USA.
This article was published in the following journal.
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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.
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.
A malignant neoplasm of the germinal tissue of the GONADS; MEDIASTINUM; or pineal region. Germinomas are uniform in appearance, consisting of large, round cells with vesicular nuclei and clear or finely granular eosinophilic-staining cytoplasm. (Stedman, 265th ed; from DeVita Jr et al., Cancer: Principles & Practice of Oncology, 3d ed, pp1642-3)
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An antibody is a protein produced by the body's immune system when it detects harmful substances, called antigens. Examples of antigens include microorganisms (such as bacteria, fungi, parasites, and viruses) and chemicals. Antibodies may be produc...