B cell development in the bone marrow is a highly regulated process and expression of a functional pre-BCR represents a crucial checkpoint, common to human and mouse. In this review, we discuss pre-BCR analogies and differences between the two species leading to pre-B cell differentiation and proliferation. In addition, the mechanisms triggering pre-BCR activation are reviewed, taking into account the recent report of heparan sulfates and galectin 1 as stromal cell-derived pre-BCR ligands. Finally, ligand-induced pre-BCR activation models are proposed on the bases of the differences reported for pre-BCR and IL7 dependencies in the two species.