Pre-B Cell Receptor Assesses the Quality of IgH Chains and Tunes the Pre-B Cell Repertoire by Delivering Differential Signals

Abstract

It is well understood how a variety of Ig H and L chains, components of BCR, are generated in the DNA level during B cell development. However, it has remained largely unknown whether and how each component is monitored for its quality and selected before the assembly into the BCR. Here we show that μH chains produced by pre-B cells display a wide spectrum of ability to form the pre-BCR, which is composed of μH and surrogate light (SL) chains and is crucial for B cell development. The level of surface pre-BCR expression varies among pre-B cells, depending on the ability of their μH chains to pair with SL chains. The higher the level of pre-BCR expression by pre-B cells, the stronger their pre-BCR signaling, and the better they proliferate and differentiate. Thus, the extent of survival, proliferation, and differentiation of individual pre-B cells is primarily determined by the SL-pairing ability of their μH chains. Furthermore, IgH chains with higher potential to assemble with IgL chains appear to be positively selected and amplified through the assessment of their ability to pair with SL chains at the pre-BCR checkpoint before the assembly into the BCR. These results indicate that the pre-BCR assesses the quality of μH chains and tunes the pre-B cell repertoire by driving the preferential expansion and differentiation of cells with the higher quality of μH chains.

A Novel Mechanism for the Autonomous Termination of Pre-B Cell Receptor Expression via Induction of Lysosome-Associated Protein Transmembrane 5

“…rable (ϳ2-to 2.5-fold). This can be explained by the facts that the former cells express a selected H chain (H Hi ), which confers the highest level of pre-BCR on pro-B cells (18), and were cultured with IL-7, which kept cells alive and also increased the pre-BCR expression level.…”

“…The culture supernatants were collected 48 h later and used to infect cells in the presence of 1 g/ml Polybrene in 24-well plates. The retroviral infection of bone marrow pro-B cells was performed as previously described (18). Quantitative RT-PCR analysis.…”

Core Fucosylation of μ Heavy Chains Regulates Assembly and Intracellular Signaling of Precursor B Cell Receptors

“…very important role to form the pre-BCR, which is composed of HC and SLC (22). The C H 1 of HC reportedly contained the N-linked glycosylation site N 46 , and the conserved N 46 -glycosylation site is important for pre-BCR function (11).…”

“…Antibodies-FITC-labeled anti-IgM (II/41), anti-erythroid (TER-119), anti-CD79b (HM79-16), PE-labeled anti-CD43 (S7), anti-IgD (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26), PE-Cy5-labeled anti-CD19 (MB19-1), anti-Gr-1 (RB6 -8C5), and APC-labeled anti-CD11b (Mac-1, M1/70) and anti-CD45R (RA3-6B2) monoclonal antibody (mAb) were obtained from e-Bioscience. Biotin-conjugated anti-mouse pre-BCR mAb (SL156), streptavidin-PE Cy5, and 5 (LM34) were purchased from BD Bioscience.…”

MAP Kinase Cascades in Antigen Receptor Signaling and Physiology

“…Moreover, introduction of exogenous μH into Rag-deficient pro-B cells resulted in the formation of surface pre-BCR (Kawano, Yoshikawa, Minegishi, & Karasuyama, 2006), which is associated with an increased phosphorylation level of ERK and initiation of pro-B cell division. MEK inhibitor U0126 treatment completely abrogated ERK phosphorylation as well as cell proliferation of μH-introduced Rag-deficient pro-B cells, indicating ERK is a direct target of pre-BCR signaling and MEK is the only upstream MAPKK for ERK activation in the pre-BCR signaling pathway associated with cell proliferation (Yasuda et al, 2008) (Yasuda et al, 2008) (Fig.…”