Transcription factors regulating B cell fate in the germinal centre

Abstract

SummaryDiversification of the antibody repertoire is essential for the normal operation of the vertebrate adaptive immune system. Following antigen encounter, B cells are activated, proliferate rapidly and undergo two diversification events; somatic hypermutation (followed by selection), which enhances the affinity of the antibody for its cognate antigen, and classswitch recombination, which alters the effector functions of the antibody to adapt the response to the challenge faced. B cells must then differentiate into antibody-secreting plasma cells or long-lived memory B cells. These activities take place in specialized immunological environments called germinal centres, usually located in the secondary lymphoid organs. To complete the germinal centre activities successfully, a B cell adopts a transcriptional programme that allows it to migrate to specific sites within the germinal centre, proliferate, modify its DNA recombination and repair pathways, alter its apoptotic potential and finally undergo terminal differentiation. To co-ordinate these processes, B cells employ a number of 'master regulator' transcription factors which mediate wholesale transcriptomic changes. These master transcription factors are mutually antagonistic and form a complex regulatory network to maintain distinct gene expression programs. Within this network, multiple points of positive and negative feedback ensure the expression of the 'master regulators', augmented by a number of 'secondary' factors that reinforce these networks and sense the progress of the immune response. In this review we will discuss the different activities B cells must undertake to mount a successful T cell-dependent immune response and describe how a regulatory network of transcription factors controls these processes.

Metabolic Regulation of the Immune Humoral Response

“…The transcription factors Bach2, Pax5 and Foxo1 act in concert with Bcl6 and antagonize plasma cell differentiation (Recaldin and Fear, 2016), whereas E2A and E2-2 transcription factors are required to drive the GC reaction as well as plasma cell differentiation (Gloury et al, 2016; Quong et al, 1999; Wohner et al, 2016) (Table 1). The contribution of these factors to cellular metabolism in B cells remains to be elucidated.…”

Fra1 Controls Rheumatoid Factor Autoantibody Production by Bone Marrow Plasma Cells and the Development of Autoimmune Bone Loss

“…Fos members of the AP‐1 transcription factor (c‐Fos and Fra1) become upregulated quickly upon B‐cell activation after antigen engagement by pathogens . Fra1 acts as a key suppressor of B‐cell differentiation into plasma cells.…”

Host response genes associated with nodular gastritis in Helicobacter pylori infection

“…After replication of SHM, GC B cells, referred to as centroblasts, acquire the production of higher affinity antibodies. In the process, GC B cells must then differentiate into antibody‐secreting plasma cells or memory B cells . After secretion of antigen‐specific IgG has occurred by plasma cells, some memory B cells reside adjacent to contracted GC.…”