Murine V lambda x and V lambda x-containing antibodies bind human myelin basic protein.

Galin, F. Shawn; Maier, Curtis C.; Zhou, Shuang; Whitaker, John N.; Blalock, J. Edwin

doi:10.1172/jci118439

Cited by 12 publications

(10 citation statements)

References 29 publications

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“…As discussed above, we think that DNA and/or MBP binding can result from incomplete editing. For example, the Asp-rich λx editor in association with H chains including 56R binds MBP ( 40 , 41 , and unpublished data). The acidic property of λx to which we attribute the MBP activity is also a feature of κ editors, and these L chains might also confer MBP activity to 56R.…”

Section: Discussionmentioning

confidence: 94%

Light chain editing generates polyreactive antibodies in chronic graft-versus-host reaction

Witsch

Chen

Fukuyama

et al. 2006

The Journal of Experimental Medicine

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The chronic graft-versus-host (cGvH) reaction is a model of induced lupus caused by alloreactive CD4+ T cells from a Bm-12 mouse in a C57BL/6 recipient. We used this cGvH reaction in C57BL/6 anti-DNA H chain transgenic mice, 56R/B6, to understand the structure, specificity, and origin of the induced autoantibodies (auto-Abs). We found anti-DNA Abs that reacted to several different antigens, such as phosphatidylserine, myelin basic protein, thyroglobulin, histone, insulin, cytochrome C, and β-galactosidase. This polyreactivity was found for Abs from B cells that expressed the 56R H chain transgene with “editor” L chains that did not completely veto autoreactivity. We suggest that such incomplete editing results in polyreactivity and that incompletely edited polyreactive B cells influence the subsequent expression of pathogenic auto-Abs in disease. We also found B cells that coexpress κ and λ L chain. These B cells contributed to the autoimmune response and are possibly in the marginal zone of the spleen.

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Section: Discussionmentioning

confidence: 94%

Light chain editing generates polyreactive antibodies in chronic graft-versus-host reaction

Witsch

Chen

Fukuyama

et al. 2006

The Journal of Experimental Medicine

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“…S2). Interestingly, the heavy chain isotype distribution of Vlx-bearing antibodies in normal mouse serum, upon immunization with myelin basic protein, showed a bias toward g2a and 2b isotypes (47). The heavy chain of Fab RY79-90 belongs also to the IgG2b isotype.…”

Section: Resultsmentioning

confidence: 99%

“…S2). It has been suggested that this unusual light chain confers specificity to the antibodies that contain it (47). As shown below, CDRL3 is a major determinant of antigen recognition.…”

Section: Resultsmentioning

confidence: 99%

Dissociation of the Dimer of the Intrinsically Disordered Domain of RNase Y upon Antibody Binding

Hardouin

Velours

Bou‐Nader

et al. 2018

Biophysical Journal

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Although RNase Y acts as the key enzyme initiating messenger RNA decay in Bacillus subtilis and likely in many other Gram-positive bacteria, its three-dimensional structure remains unknown. An antibody belonging to the rare immunoglobulin G (IgG) 2b lx isotype was raised against a 12-residue conserved peptide from the N-terminal noncatalytic domain of B. subtilis RNase Y (BsRNaseY) that is predicted to be intrinsically disordered. Here, we show that this domain can be produced as a stand-alone protein called Nter-BsRNaseY that undergoes conformational changes between monomeric and dimeric forms. Circular dichroism and size exclusion chromatography coupled with multiangle light scattering or with small angle x-ray scattering indicate that the Nter-BsRNaseY dimer displays an elongated form and a high content of a-helices, in agreement with the existence of a central coiled-coil structure appended with flexible ends, and that the monomeric state of Nter-BsRNaseY is favored upon binding the fragment antigen binding (Fab) of the antibody. The dissociation constants of the IgG/BsRNaseY, IgG/Nter-BsRNaseY, and IgG/peptide complexes indicate that the affinity of the IgG for Nter-BsRNaseY is in the nM range and suggest that the peptide is less accessible in BsRNaseY than in Nter-BsRNaseY. The crystal structure of the Fab in complex with the peptide antigen shows that the peptide adopts an elongated U-shaped conformation in which the unique hydrophobic residue of the peptide, Leu6, is completely buried. The peptide/Fab complex may mimic the interaction of a microdomain of the N-terminal domain of BsRNaseY with one of its cellular partners within the degradosome complex. Altogether, our results suggest that BsRNaseY may become accessible for protein interaction upon dissociation of its N-terminal domain into the monomeric form. FIGURE 1 Characterization of a monoclonal antibody induced against a 12-residue peptide of Nter-BsRNaseY. (A) Sequence alignment of the N-terminal domains of RNases Y from B. subtilis, Staphylococcus aureus, Streptococcus pyogenes, Listeria monocytogenes, Clostridium perfringens, Lactoccus lactis, Borrelia burgdorferi, and Leadbetterella byssophila was performed with Clustal Omega (67) and rendered with ESPript (68). The predicted N-terminal TM helix (residues 6-24) and the inducing peptide (residues 79-90) are indicated. (B) Recognition of BsRNaseY by IgG RY79-90 as detected by immunoblotting (legend continued on next page) Fab Binding Dissociates RNase Y IDD Biophysical Journal 115, 2102-2113, December 4, 2018 2103Protein stoichiometry analysis of the Nter-BsRNaseY/Fab RY79-90 complex (at a 1:2 ratio) was performed by SEC-MALS using the ''UV extinction from RI peak'' method (28) and the protein conjugate method (29) (see Supporting Materials and Methods). In the first method, the UV 280 extinction coefficients of the peaks are extracted from the SEC-MALS data and compared to the predicted extinction coefficients Fab Binding Dissociates RNase Y IDD (C) Structural models of Nter-BsRNaseY. Top: Two at...

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“…The mouse λX L-chain has been shown to bind the self-antigen myelin basic protein alone or in combination with V H s (Doyle et al, 2006; Galin et al, 1996). This may account for the low expression of λX observed in wild-type mice (Li et al, 2004).…”

Section: 0 Discussionmentioning

confidence: 99%

B cell receptor light chain repertoires show signs of selection with differences between groups of healthy individuals and SLE patients

Schoettler¹,

Ni²,

Weigert³

2012

Molecular Immunology

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We have developed a microarray to study the expression of L-chain V genes (VL genes) in healthy and SLE patient peripheral κ- and λ-sorted B cells. In all repertoires tested, one VL gene accounts for over 10% of all gene VL expression, consistent with positive selection acting on L-chains. While a few VL genes were highly expressed in all individuals, most VL genes were expressed at different levels. Some VL genes (5 out of a total of 78) were not detected. We attribute their absence from the repertoire to negative selection. Positive selection and negative selection were also found in SLE repertoires, but expression of VL genes was different; the differences point to less regulation of VL gene repertoires in SLE. Our data shows that VL gene expression is variable and supports a model where the L-chain repertoire is generated by both positive and negative selection on L-chains.

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Murine V lambda x and V lambda x-containing antibodies bind human myelin basic protein.

Cited by 12 publications

References 29 publications

Light chain editing generates polyreactive antibodies in chronic graft-versus-host reaction

Light chain editing generates polyreactive antibodies in chronic graft-versus-host reaction

Dissociation of the Dimer of the Intrinsically Disordered Domain of RNase Y upon Antibody Binding

B cell receptor light chain repertoires show signs of selection with differences between groups of healthy individuals and SLE patients

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