Brief Definit ive Report

B cell development is a tightly controlled pro cess that promotes the survival and expansion of B cells with affinity for invading organisms while eliminating autoreactive B cells and thereby preventing autoimmunity (Browning, 2006; Allman and Pillai, 2008). The recent clinical success of B cell targeted therapies in a multi tude of autoimmune disorders has highlighted the potential role of B cells in disease pathology. Work in the last several decades has also revealed that B cells have alternative effector functions in addition to antibody production, and can play a role in the pathology of a multitude of human diseases and provide additional thera peutic intervention points (Browning, 2006; Gürcan et al., 2009). Although much has been discovered about lymphocyte development and activation through the use of traditional gene targeting approaches, it also has its limitations. These include require ments for a gene in embryonic development, the development of a particular cell type, or a hy pothesis that a gene is involved in the function of a particular cell type or pathway. Forward ge netic approaches have classically proven to be valuable tools in many model organisms, and work from the last 10 years has shown that it can also be a useful tool in mice (Beutler et al., 2006; Cook et al., 2006). Random mutagenesis also provides the opportunity to identify mutants with reduced or increased activity as opposed to full ablation, which can provide insight into how a particular molecule is functioning. To this end, we used a forward genetic screen using NethylNnitrosourea (ENU)– induced mutagenesis in mice to identify novel regulators of immune function. We discovered