Figure 1.

Ikaros controls multiple levels of B cell lymphopoiesis and function. A: Ikaros plays a crucial role in the specification of the B cell lineage by promoting the expression of the IL-7R and Flt3 receptors in common lymphoid progenitors (CLPs) and of the EBF transcription factor in pre-pro-B cells. Later, Ikaros regulates Igh recombination by activating Rag gene expression and contracting the Igh locus. After the preBCR check point, Ikaros also downregulates the expression of the preBCR component, Lambda5. During light-chain rearrangment, it is thought that Ikaros regulates allelic exclusion; B: In the periphery, Ikaros sets the B cell activation threshold to antigen and T cell co-stimulation, and inhibits hyper-proliferation of activated B cells. Finally, during class switch recombination, Ikaros controls isotype choice by inhibiting switching to IgG2b and IgG2a and promoting switching to all other isotypes.