Cutting edge:: Signaling and cell surface expression of a μH chain in the absence of λ5:: A paradigm revisited

Pre-B cell receptor (pre-BCR) signals are essential for pro-B cells to mature efficiently into pre-B cells. The pre-BCR is an Ig-Iike transmembrane complex that is assembled from two muH chains (muHC) and two surrogate L chains consisting of the non-covalently associated polypeptides VpreB and lambda5. In lambda5(-/-) mice, pro-B cell maturation is impaired, but not completely blocked implying that a muHC induces differentiation signals in the absence of lambda5. Using a mouse model, in which transgenic muHC expression can be controlled by tetracycline, we show that in the absence of lambda5, the transgenic muHC promotes in vivo differentiation of pro-B cells, induces IL-7-dependent cell growth, and is expressed on the surface of pre-B cells. Our findings not only show that an incomplete pre-BCR can initiate signals, but also challenge the paradigm that an IgHC must associate with an IgLC or a SLC to gain transport and signaling competency.