BAFF and the plasticity of peripheral B cell tolerance

BAFF and its receptors play a crucial role in peripheral B cell selection and survival, by dictating the set point for mature primary B cell numbers and adjusting thresholds for specificity-based selection during transitional differentiation. The notion that selective stringency can be varied on the basis of homeostatic demands reveals a previously unappreciated degree of plasticity in B cell tolerance, and suggests a paradigm that unites peripheral negative and positive selection with the maintenance of mature B cell numbers. Moreover, it implies a developmentally regulated coupling of BCR and BAFF receptors at the transitional stages and beyond.