The pre-BCR checkpoint as a cell-autonomous proliferation switch

Early in B-cell development, productive V(D)J recombination leads to synthesis of the membrane Ig heavy (H)-chain protein μ, which associates with the surrogate light (L)-chain proteins λ5 and VpreB to form the pre-B-cell receptor (pre-BCR). Pre-BCR expression serves as a checkpoint that monitors for functional Ig H-chain rearrangement and triggers clonal expansion and developmental progression of Igμ+ pre-B cells. Recent intriguing observations have shed new light on the apparently constitutive ligand-independent signalling capacity of the pre-BCR and the unexpected roles of the downstream signalling molecules SLP-65 and Btk, which limit pre-B-cell proliferation and thereby act as tumour suppressors. Taken together, these observations indicate that the pre-BCR checkpoint functions as a cell-autonomous proliferation switch.