Bcl6: where too much complexity is barely enough

Appropriate B-cell differentiation in response to antigen is fundamental to health. Central to the regulation of this process in circumstances of T-cell-dependent immune responses is the transcriptional repressor Bcl6, which is required for germinal centre (GC) formation and function. Within GCs, Bcl6 is already known to regulate many functions including proliferation, assessing DNA damage and terminal differentiation. Targets of Bcl6 repression in B cells have been identified in a variety of systems with some, such as the reciprocal regulation of the Prdm1 gene encoding Blimp1, being particularly well studied and in effect becoming a model for the counter-regulation of Bcl6 and Blimp1 in a variety of cell types. A study in this issue of the European Journal of Immunology examines the regulatory network of Bcl6 in DT40, a chicken lymphoma, and reproduces some of the complexity of other species but also adds new targets for Bcl6 regulation, genes involved in class switch recombination and somatic hypermutation. While this increasing complexity may be daunting, it emphasises the critical importance of understanding how Bcl6 may integrate the multitude of processes occurring in GCs.