title: Germinal center B-cells.
abstract: 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 (T(FH)) 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.
authors.affiliation: Department of Medicine, Section of Rheumatology and Gwen Knapp Center for Lupus and Immunology Research, The University of Chicago, Chicago, Illinois 60637, USA. Khamel@medicine.bsd.uchicago.edu
authors.forename: Keith M
authors.initials: KM
authors.lastname: Hamel
authors.forename: Vladimir M
authors.initials: VM
authors.lastname: Liarski
authors.forename: Marcus R
authors.initials: MR
authors.lastname: Clark
mesh_terms: D000818:Animals; D000941:Antigens / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D018858:Germinal Center / Q000276:immunology*; D006801:Humans; D007154:Immune System Diseases / Q000276:immunology; D007156:Immunologic Memory; D008213:Lymphocyte Activation / Q000276:immunology; D008221:Lymphoid Tissue / Q000276:immunology; D010950:Plasma Cells / Q000166:cytology / Q000276:immunology
chemical_list: D000941:Antigens