Biology of Germinal Center B Cells Relating to Lymphomagenesis.
Abstract
The germinal center (GC) reaction is a key feature of adaptive humoral immunity. GCs represent the site where mature B cells refine their B-cell receptor (BCR) and are selected based on the newly acquired affinity for the antigen. In the GC, B cells undergo multiple cycles of proliferation, BCR remodeling by immunoglobulin somatic hypermutation (SHM), and affinity-based selection before emerging as effector memory B cells or antibody-secreting plasma cells. At least 2 histologically and functionally distinct compartments are identified in the GC: the dark zone (DZ) and the light zone (LZ). The proliferative burst and immunoglobulin remodeling by SHM occur prevalently in the DZ compartment. In the LZ, GC B cells undergo an affinity-based selection process that requires the interaction with the antigen and accessory cells. GC B cells are also targeted by class switch recombination, an additional mechanism of immunoglobulin remodeling that ensures the expression of diverse isotype classes. These processes are regulated by a complex network of transcription factors, epigenetic modifiers, and signaling pathways that act in concert with mechanisms of intra-GC B-cell trafficking. The same mechanisms underlying the unique ability of GC...Continue Reading
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