| First Author | Sun L | Year | 2018 |
| Journal | Biochem Biophys Res Commun | Volume | 495 |
| Issue | 1 | Pages | 1411-1417 |
| PubMed ID | 29191653 | Mgi Jnum | J:270710 |
| Mgi Id | MGI:6277590 | Doi | 10.1016/j.bbrc.2017.11.171 |
| Citation | Sun L, et al. (2018) Distorted antibody repertoire developed in the absence of pre-B cell receptor formation. Biochem Biophys Res Commun 495(1):1411-1417 |
| abstractText | The pre-B cell receptor (pre-BCR), consisting of the mu heavy chain (muHC) and the surrogate light chain (SLC, Vpre-B and lambda5), plays important roles during B cell development. The formation of the pre-BCR, which enables the nascent immunoglobulin HC to associate with the SLC, is considered a prerequisite for B cell development. However, a significant number of peripheral mature (leaky) B cells exist in SLC-deficient mice. These leaky B cells develop in the absence of pre-BCR and do not undergo the pre-BCR checkpoint. The antibody repertoires of leaky B cells thus reflect the absence of pre-BCR function. To investigate how the absence of the pre-BCR is circumvented by these leaky-B cells and examine the effect of the pre-BCR checkpoint on the antibody system, we analyzed the antibody repertoires of lambda5-deficient (lambda5(-/-)) mice using next-generation sequencing. In lambda5(-/-) mice, spleen B cells displayed different patterns of VDJ-usage, relative to those in wild-type (WT) mice. Moreover, leaky B cells were neither derived from unusual B2 cells, characterized by particular LC gene rearrangements in the absence of pre-BCR signaling, nor from B1 cells, originating from different B cell progenitors. Analysis of the CDR-H3 amino acid sequences of mu-chain repertoires revealed that certain bone marrow B cells with particular CDR-H3 profiles undergo clonal expansion in lambda5(-/-) mice. Part of these CDR-H3s contain arginine(s) in the middle of the CDR-H3 loop in lambda5(-/-) mice, whereas few arginine(s) exist in this middle loop in WT CDR-H3s in the absence of clonal expansion. This CDR-H3 feature in lambda5(-/-) mice presumably reflects the role of the pre-BCR in autoantibody regulation, since arginine(s) are often found in the antigen-binding site of autoantibodies. Here, we present a unique viewpoint on the role of pre-BCR, by assessing the whole antibody repertoire formed in SLC-deficient mice. |
