Review article: role of the surrogate light chain and the pre-B-cell receptor in mouse B-cell development.

Abstract

The generation of B lymphocytes from committed progenitor cells is a complex process involving the transit of cells through several critical stages of development. Throughout their transit, developing B cells are subject to choices between survival, proliferation or death; fates that are dictated by combinations of intrinsic and extrinsic signals. Thus, failure to express certain signalling molecules on their surface at particular stages of development results in the cell failing to receive a viability and/or proliferative signal. Likewise, failure to link surface receptor expression to survival machinery will result in cell death. During the early stages of B-cell development, one such receptor molecule is the pre-B-cell receptor (pre-BCR). The pre-BCR is a heterodimer composed of an immunoglobulin (Ig) heavy chain molecule (IgH) covalently associated with an immunoglobulin light chain-like molecule called the surrogate light chain (SL).1–3 The SL itself is made up of two non-covalently associated proteins called lambda-5 (λ5) and VpreB, which together form a molecule having structural homology with conventional light (IgL) chains.4,5 Thus, in the SL, λ5 replaces a light chain constant region and VpreB the variable part. It is likely that the membrane pre-BCR complex is composed of two IgH molecules associated with two SLs.1 However, SL can reach the surface in the absence of IgH but in association with other molecules, for example with a glycoprotein of approximately 130 000 MW, so-called gp130.6,7 In this case, the surface SL-containing complex is referred to as a pro-BCR.8 The detailed description of SL structure must await crystallographic analysis, but recently Melchers has proposed a model of SL chain assembly.9 In this review we will discuss the molecular structure and gene organization of pre-BCR components and attempt to outline how surface expression of the pre-BCR impacts on cell survival, differentiation, proliferation and repertoire selection of developing B cells. General scheme of B lymphocyte development Different stages of B-cell development can be defined by the use of a combination of cell-surface markers and the status of immunglobulin gene rearrangements10,11 (Fig. 1, B-lymphocyte development in adult bone marrow). Following commitment to the B-cell lineage, an event which is still poorly understood, the first stage of the B-cell lineage is called a pro-B cell and is defined phenotypically as a B220+CD19− c-kit+CD43+CD25−IgM−IgD− cell in which there does not have to be any immunoglobulin gene rearrangement.12,13 It should be noted though that some pro-B cells have DJH rearrangements but only on one allele.13 Thus pro-B cells are found in mice in which the recombinase-activating genes (RAG) have been deleted,14,15 and in such mice, they are CD19+. However, pro-B cells do contain RNA transcripts for components of the SL but it is unclear at the present time whether they contain SL protein either in their cytoplasm or at the cell surface.13,16 It is possible that SL might reach the cell surface in association with molecules other than IgH, for example gp130.6,7 Open in a separate window Figure 1 B-lymphocyte development in the adult mouse bone marrow.