Uncoupling of Natural IgE Production and CD23 Surface Expression Levels

Ren, Weicheng; Lagerstedt, Kristina; Grimsholm, Ola; Stern, Anna; Sun, Jiabin; Fang, Yanwen; Zou, Xiang; Mårtensson, Inga‐Lill

doi:10.1371/journal.pone.0062851

Cited by 2 publications

(1 citation statement)

References 32 publications

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“…Spleens from SLC −/− mice were collected and embedded in OCT compound (TissueTek, Tokyo, Japan), snap-frozen in liquid nitrogen, and stored at −80°C. Frozen sections (8 μm) were cut using a cryostat (Wetzlar, Germany), and stained (Supporting Information Table 1) as previously described [47]. Images were acquired using an LSM 700 confocal microscope and ZEN 2009 acquisition software (Zeiss, Germany).…”

Section: Immunohistochemistrymentioning

confidence: 99%

Surrogate light chain is required for central and peripheral B‐cell tolerance and inhibits anti‐DNA antibody production by marginal zone B cells

et al. 2015

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Selection of the primary antibody repertoire takes place in pro-/pre-B cells, and subsequently in immature and transitional B cells. At the first checkpoint, μ heavy (μH) chains assemble with surrogate light (SL) chain into a precursor B-cell receptor. In mice lacking SL chain, μH chain selection is impaired, and serum autoantibody levels are elevated. However, whether the development of autoantibody-producing cells is due to an inability of the resultant B-cell receptors to induce central and/or peripheral B-cell tolerance or other factors is unknown. Here, we show that receptor editing is defective, and that a higher proportion of BM immature B cells are prone to undergoing apoptosis. Furthermore, transitional B cells are also more prone to undergoing apoptosis, with a stronger selection pressure to enter the follicular B-cell pool. Those that enter the marginal zone (MZ) B-cell pool escape selection and survive, possibly due to the B-lymphopenia and elevated levels of B-cell activating factor. Moreover, the MZ B cells are responsible for the elevated IgM anti-dsDNA antibody levels detected in these mice. Thus, the SL chain is required for central and peripheral B-cell tolerance and inhibits anti-DNA antibody production by MZ B cells.Keywords: Autoantibodies r Autoimmunity r Light chain recombination r Marginal zone B cells r Pre-BCR Additional supporting information may be found in the online version of this article at the publisher's web-site Introduction V(D)J recombination is a stochastic process that gives rise to a vast primary repertoire of B-cell receptors (BCRs), recognizing self (auto) and nonself antigens. To purge and control autoreactive B cells, several checkpoints are in place, in both central and peripheral lymphoid organs [1,2]. The main mechanism of central B-cell tolerance is receptor editing [3,4] and, as some autoreactivity remains among the cells that migrate to the periphery [5], they undergo further selection as transitional B cells in the spleen Correspondence: Prof. Inga-Lill Mårtensson e-mail: lill.martensson@rheuma.gu.se[6], mainly by clonal deletion. Extrinsic factors are also involved, for example, B lymphocyte activating factor (BAFF), also known as BLyS, a key factor that modulates survival of peripheral B cells [7]. Defective central and peripheral B-cell tolerance checkpoints, as well as elevated BAFF levels have all been associated with autoimmune diseases, for example, systemic lupus erythematosus and rheumatoid arthritis, and mouse models thereof, a hallmark of which is autoantibody production [8][9][10].Selection of the primary BCR repertoire takes place also at the pro-B to pre-B-cell transition based on antibody μ heavy (μH) * These authors contributed equally to this work. and κ germline configuration (GL) and λ2 germline transcripts (λ2 0 ) and λ1,2,3 rearrangements (RE). (E) Rag-1 and Rag-2 mRNA levels. Data are shown as mean ± SEM of three to five mice per group, and are from a single experiment representative of three independent experiments. p Values were determine...

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Section: Immunohistochemistrymentioning

confidence: 99%