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

Abstract

AbstractThe development of early precursor B cells is governed by the surface‐bound pre‐B cell receptor consisting of the immunoglobulin μ heavy chain, the surrogate light chain components λ5 and VpreB, and the signal transducing subunits immunglobulin α/immunglobulin β. The pre‐B cell receptor controls clonal expansion, survival and efficient differentiation of functional B lymphoid precursors; however, it is still controversial how signals from this receptor are initiated. Recent studies with 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). Strikingly however, 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 galectin‐1. Even though these findings are not mutually exclusive, they refresh the discussion about potential modes of pre‐BCR signal initiation. In this review, we discuss recent key findings and propose an integrative model for ligand dependent and independent initiation of pre‐BCR signals during selection of functional B cell precursors.