Mice deficient in the transcription factor BOB1 (also known as POU2AF1) have defective B cell responses and lack germinal centres and marginal zone B cells. These findings have led to the suggestion that BOB1 potentiates B cell receptor (BCR) signalling. By identifying novel transcriptional targets of BOB1, Lindner et al. offer an alternative explanation for the immunodeficiency seen in BOB1-deficient mice. They show that BOB1 regulates the expression of the microRNAs miR-146a and miR-210, which are known to negatively regulate B cell signalling pathways. Thus, they propose that B cells that lack BOB1 may receive excessively strong BCR signals during their development, which leads to the induction of an anergic-like state. In support of this idea, they found that peripheral B cells in BOB1-deficient mice have an anergic phenotype.