The Non-Ig Parts of the VpreB and l5 Proteins of the Surrogate Light Chain Play Opposite Roles in the Surface Representation of the Precursor B Cell Receptor

The VpreB and l5 proteins, together with Igm-H chains, form precursor BCRs (preBCRs). We established l5 2/2 /VpreB1 2/2 / VpreB2 2/2 Abelson virus-transformed cell lines and reconstituted these cells with l5 and VpreB in wild-type form or with a deleted non-Ig part. Whenever preBCRs had the non-Ig part of l5 deleted, surface deposition was increased, whereas deletion of VpreB non-Ig part decreased it. The levels of phosphorylation of Syk, SLP65, or PLC-g2, and of Ca 2+ mobilization from intracellular stores, stimulated by mH chain crosslinking Ab were dependent on the levels of surface-bound preBCRs. It appears that VpreB probes the fitness of newly generated VH domains of IgH chains for later pairing with IgL chains, and its non-Ig part fixes the preBCRs on the surface. By contrast, the non-Ig part of l5 crosslinks preBCRs for downregulation and stimulation. T he precursor BCR (preBCR) is composed of two identical Igm-H chains and two surrogate L chains (SLC) (1, 2). PreBCRs are selectively expressed during preB cell development on large preB II cells that have undergone productive V H to D H J H rearrangements on the IgH chain locus and express a mH chain capable of pairing with SLC (3, 4). More than half of the in-frame V H D H J H rearrangements do not pair with the SLC. Therefore, cells expressing such mH chains do not form a preBCR on their surface (5). The SLC is composed of VpreB (either VpreB1 or VpreB2) and l5 proteins that associate noncovalently into an Ig L chain-like structure, because both VpreB and l5 have Ig domain-like structures (6). VpreB lacks the seventh b sheet in its Ig domain, whereas l5 has an additional b sheet within the aminoterminal portion extending beyond its Ig domain. Deletion of this additional b sheet in l5 abolishes the capacity of VpreB and l5 to form a non-covalently bound L chain-like structure, suggesting that the extra b sheet of l5 occupies the structural features of the seventh b sheet of a classical Ig-V domain in VpreB (7). Both VpreB and l5 also have non-Ig–like structures, VpreB at its C-terminal end and l5 at its N-terminal end. The experiments of Minegishi et al. (7) have suggested that the non-Ig part of l5 acts as a chaperone in the assembly of the preBCR. Without VpreB, the non-Ig part-containing wild-type form of l5 cannot form disulphide bonds between the …