The epigenetic regulation of the germinal center response

Abstract

In response to T-cell-dependent antigens, antigen-experienced B cells migrate to the center of the B-cell follicle to seed the germinal center (GC) response after cognate interactions with CD4+ T cells. These GC B cells eventually mature into memory and long-lived antibody-secreting plasma cells, thus generating long-lived humoral immunity. Within GC, B cells undergo somatic hypermutation of their B cell receptors (BCR) and positive selection for the emergence of high-affinity antigen-specific B-cell clones. However, this process may be dangerous, as the accumulation of aberrant mutations could result in malignant transformation of GC B cells or give rise to autoreactive B cell clones that can cause autoimmunity. Because of this, better understanding of GC development provides diagnostic and therapeutic clues to the underlying pathologic process. A productive GC response is orchestrated by multiple mechanisms. An emerging important regulator of GC reaction is epigenetic modulation, which has key transcriptional regulatory properties. In this review, we summarize the current knowledge on the biology of epigenetic mechanisms in the regulation of GC reaction and outline its importance in identification of immunotherapy decision making.