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Review
. 2018 Nov 15:9:2423.
doi: 10.3389/fimmu.2018.02423. eCollection 2018.

The Role of the Pre-B Cell Receptor in B Cell Development, Repertoire Selection, and Tolerance

Thomas H Winkler  1 , Inga-Lill Mårtensson  2
Affiliations
Review

The Role of the Pre-B Cell Receptor in B Cell Development, Repertoire Selection, and Tolerance

Thomas H Winkler et al. Front Immunol. .

Abstract

Around four decades ago, it had been observed that there were cell lines as well as cells in the fetal liver that expressed antibody μ heavy (μH) chains in the apparent absence of bona fide light chains. It was thus possible that these cells expressed another molecule(s), that assembled with μH chains. The ensuing studies led to the discovery of the pre-B cell receptor (pre-BCR), which is assembled from Ig μH and surrogate light (SL) chains, together with the signaling molecules Igα and β. It is expressed on a fraction of pro-B (pre-BI) cells and most large pre-B(II) cells, and has been implicated in IgH chain allelic exclusion and down-regulation of the recombination machinery, assessment of the expressed μH chains and shaping the IgH repertoire, transition from the pro-B to pre-B stage, pre-B cell expansion, and cessation.

Keywords: B-cell development; VpreB; allelic exclusion; pre-B cells; surrogate light chain; λ-5.

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Figures

Figure 1
Figure 1
The pre-B cell receptor (pre-BCR). A pre-BCR is assembled from antibody heavy (μH) and surrogate light chains together with the signaling molecules Igα and Igβ. The SL chain is composed of VpreB1/2 and λ5. VpreB and λ5 each contains a unique region, depicted as tails protruding from the respective molecule.
Figure 2
Figure 2
Simplified scheme of B cell development in wild type and SL chain knockout mice. At the pro-B cell stage, several cell divisions take place (not shown) and both alleles of the IgH locus will finally become DJH-rearranged. A functional VHDJH rearrangement will code for a μH chain assembling with the SL chain. The pre-BCR induces proliferative expansion of pre-B cells, which is missing in SL chain knockout mice. During the proliferative expansion, expression of the genes encoding SL chain is downregulated and the SL chain protein disappears from the cell. When pre-B cells leave the cell cycle and become small pre-B cells, light chain genes are rearranged that encode for a light chain protein forming a B cell receptor with the selected μH chain. Five cell divisions at the pre-B cell stage are depicted, leading to 32-fold higher output of B cells in wild type vs. SL knockout mice. See text for further details.
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