Antibodies that bind complex glycosaminoglycans accumulate in the Golgi

Radic, Marko; Weigert, Martin; Khan, Salar N.; Han, Julianna; Kalinina, Olga; Prak, Eline T. Luning

doi:10.1073/pnas.1308620110

Cited by 3 publications

(3 citation statements)

References 45 publications

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“…Both VλX and its closest human homologue Vλ5-1 have long L3s that contain Asp in site 96, whereas Vλ5-6 has a short L3 and no L3 Asp. As shown for VλX junctional variants, L3 is of paramount importance for editing ( Radic et al, 2013 ).…”

Section: Resultsmentioning

confidence: 99%

Light chain editors of anti-DNA receptors in human B cells

Kalinina

Wang

Sia

et al. 2014

Journal of Experimental Medicine

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Section: Resultsmentioning

confidence: 99%

Light chain editors of anti-DNA receptors in human B cells

Kalinina

Wang

Sia

et al. 2014

Journal of Experimental Medicine

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“…As to the molecular basis for enhanced Mott cell formation in FcμR-deficient mice, the possibility that FcμR may be involved in the assembly process of nascent immunoglobulin μ HCs in the ER is unlikely because IgG + Mott cells were also observed, albeit less frequently, in the mutant mice. There is a precedent that certain B-cell hybridomas accumulate IgM in the Golgi due to formation of IgM/glycosaminoglycan complexes and release of large spherical IgM complexes, termed spherons, of up to 2 μm in diameter (51,52). Thus, it is possible that some of the IgM produced by plasma cells in both groups (B6/lpr and B6) of FcμR(−) mice may recognize determinant(s) on the ER membrane, thereby generating Mott cells.…”

Section: Discussionmentioning

confidence: 99%

Enhanced auto-antibody production and Mott cell formation in FcμR-deficient autoimmune mice

Honjo

Kubagawa

Suzuki

et al. 2014

International Immunology

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The IgM-Fc receptor (FcμR) is involved in IgM homeostasis as evidenced by increased pre-immune serum IgM and natural auto-antibodies of both IgM and IgG isotypes in Fcmr-deficient C57BL/6 (B6) mice. To determine the impact of Fcmr-ablation on autoimmunity, we introduced the Fcmr null mutation onto the Fas-deficient autoimmune-prone B6.MRL Fas (lpr/lpr) mouse background (B6/lpr). Both IgM and IgG auto-antibodies against dsDNA or chromatin appeared earlier in FcμR(-) B6/lpr than FcμR(+) B6/lpr mice, but this difference became less pronounced with age. Splenic B2 cells, which were 2-fold elevated in FcμR(+) B6/lpr mice, were reduced to normal B6 levels in FcμR(-) B6/lpr mice, whereas splenic B1 cells were comparable in both groups of B6/lpr mice. By contrast, marginal zone (MZ) B cells were markedly reduced in FcμR(-) B6/lpr mice compared with either FcμR(+) B6/lpr or wild type (WT) B6 mice. This reduction appeared to result from rapid differentiation of MZ B cells into plasma cells in the absence of FcμR, as IgM antibody to a Smith (Sm) antigen, to which MZ B cells are known to preferentially respond, was greatly increased in both groups (B6/lpr and B6) of FcμR(-) mice compared with FcμR(+) B6/lpr or B6 mice. Mott cells, aberrant plasma cells with intra-cytoplasmic inclusions, were also increased in the absence of FcμR. Despite these abnormalities, the severity of renal pathology and function and survival were all indistinguishable between FcμR(-) and FcμR(+) B6/lpr mice. Collectively, these findings suggest that FcμR plays important roles in the regulation of auto-antibody production, Mott cell formation and the differentiation of MZ B cells into plasma cells in B6.MRL Fas (lpr/lpr) mice.

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“…(iii) LPS or IL-5 stimulation of sorted B-1 B cells from autoimmune mice (NZB/W F 1 ) generates Mott cells ex vivo at a frequency of ~50 times higher than conventional B-2 B cells (81). (iv) In studies of autoantibody transgenic mice, incompletely edited B cells express multi-reactive IgM that accumulates in the Golgi and is released or detached from the membrane as insoluble amyloid-like immune complexes termed spherons reaching up to ~2 μm in diameter (82, 83).…”

Section: Fcμr and Mott Cell Formation In The Control Of Autoimmunity mentioning

confidence: 99%

Functional Roles of the IgM Fc Receptor in the Immune System

et al. 2019

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It is now evident from studies of mice unable to secrete IgM that both non-immune “natural” and antigen-induced “immune” IgM are important for protection against pathogens and for regulation of immune responses to self-antigens. Since identification of its Fc receptor (FcμR) by a functional cloning strategy in 2009, the roles of FcμR in these IgM effector functions have begun to be explored. Unlike Fc receptors for switched Ig isotypes (e.g., FcγRs, FcεRs, FcαR, Fcα/μR, pIgR, FcRn), FcμR is selectively expressed by lymphocytes: B, T, and NK cells in humans and only B cells in mice. FcμR may have dual signaling ability: one through a potential as yet unidentified adaptor protein non-covalently associating with the FcμR ligand-binding chain via a His in transmembrane segment and the other through its own Tyr and Ser residues in the cytoplasmic tail. FcμR binds pentameric and hexameric IgM with a high avidity of ~10 nM in solution, but more efficiently binds IgM when it is attached to a membrane component via its Fab region on the same cell surface ( cis engagement). Four different laboratories have generated Fcmr- ablated mice and eight different groups of investigators have examined the resultant phenotypes. There have been some clear discrepancies reported that appear to be due to factors including differences in the exons of Fcmr that were targeted to generate the knockouts. One common feature among these different mutant mice, however, is their propensity to produce autoantibodies of both IgM and IgG isotypes. In this review, we briefly describe recent findings concerning the functions of FcμR in both mice and humans and propose a model for how FcμR plays a regulatory role in B cell tolerance.

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Antibodies that bind complex glycosaminoglycans accumulate in the Golgi

Cited by 3 publications

References 45 publications

Light chain editors of anti-DNA receptors in human B cells

Light chain editors of anti-DNA receptors in human B cells

Enhanced auto-antibody production and Mott cell formation in FcμR-deficient autoimmune mice

Functional Roles of the IgM Fc Receptor in the Immune System

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