The pre‐B cell receptor and its ligands – it takes two to tango

DFG Training Program GK592, Nikolaus Fiebiger Center for Molecular Medicine, University ofErlangen and Nurnberg, GermanyThe development of early precursor B cells is governed by the surface-bound pre-B cell receptorconsisting of the immunoglobulin µ heavy chain, the surrogate light chain components λ5andVpreB, and the signal transducing subunits immunglobulin α/immunglobulin β. The pre-B cell re-ceptor controls clonal expansion, survival and efficient differentiation of functional B lymphoid pre-cursors; however, it is still controversial how signals from this receptor are initiated. Recent studieswith Abelson murine leukemia virus (Abl-MuLV)-transformed pre-B cell lines suggest that the N-terminal non-immunoglobulin portion of λ5, the so-called unique tail, is required to initiate cell-autonomous signals by mediating self-aggregation of the pre-B cell receptor (pre-BCR). Strikinglyhowever, the λ5 unique tail also controls the interaction with two different groups of stroma cell-derived pre-BCR ligands, namely heparan sulfate glycosaminoglycans and surface-associated ga-lectin-1. Even though these findings are not mutually exclusive, they refresh the discussion aboutpotential modes of pre-BCR signal initiation. In this review, we discuss recent key findings andpropose an integrative model for ligand dependent and independent initiation of pre-BCR signalsduring selection of functional B cell precursors.