B Cell-Intrinsic IRF4 Haploinsufficiency Impairs Affinity Maturation.

The germinal center (GC) reaction is a coordinated and dynamic ensemble of cells and processes that mediate the maturation and selection of high-affinity GC B cells (GCBs) from lower-affinity precursors and ultimately results in plasma cell and memory cell fates that exit the GC. It is of great interest to identify intrinsic and extrinsic factors that control the selection process. The transcription factor IRF4, induced upon BCR and CD40 signaling, is essential for the acquisition of plasma cell and GCB cell fates.

Protocol for BCR-mediated plasma cell differentiation and purification of chromatin-associated proteins.

Molecular-level understanding of plasma cell (PC) differentiation has been modeled using lipopolysaccharide (LPS) stimulation . However, this system does not involve the B-cell receptor (BCR)-a critical component of B cell biology. Here, we present a protocol for PC differentiation system dependent on BCR signaling that easily scales up for cell number-demanding applications, including protein complex purification.

A Synchronous IRF4-Dependent Gene Regulatory Network in B and Helper T Cells Orchestrating the Antibody Response.

Control of diverse pathogens requires an adaptive antibody response, dependent on cellular division of labor to allocate antigen-dependent B- and CD4 T-cell fates that collaborate to control the quantity and quality of antibody. This is orchestrated by the dynamic action of key transcriptional regulators mediating gene expression programs in response to pathogen-specific environmental inputs. We describe a conserved, likely ancient, gene regulatory network that intriguingly operates contemporaneously in B and CD4 T cells to control their cell fate dynamics and thus, the character of the antibody response.