Abstract
Abstract MRL/Mp(-)+/+ mice produce antinuclear antibodies and develop a spontaneous autoimmune syndrome with lupus-like nephritis. We obtained a panel of seven histone-reactive IgG mAb from a single MRL/Mp(-)+/+ mouse. These antibodies do not react significantly with DNA or individual histones, but bind strongly to the histone H2A-H2B dimer and even more strongly to the H2A-H2B-DNA complex. These antibodies also bind to whole nuclei when tested by immunofluorescence, indicating that they recognize an epitope accessible in chromatin. The V region sequences of these antibodies have been determined. The H chain third complementarity-determining regions of these antibodies are similar to those found in anti-DNA antibodies even though the antibodies in our panel do not react with DNA in the absence of histones, suggesting that DNA is part of the subnucleosome epitope. Several of these antibodies are clonally related, supporting the hypothesis that the activation of these clones is Ag-driven. Analysis of the sequences of these antibodies indicates that they derive from autoreactive B cells that were clonally expanded and whose V region genes have undergone numerous somatic mutations.
Keywords
Anti-nuclear antibodyHistoneEpitopeAntibodyBiologyAutoantibodyMolecular biologyDNAMonoclonal antibodyChromatinHistone H2BImmunologyGenetics
Related Publications
Antigenic and Immunogenic Characterization of Recombinant Baculovirus-Expressed Severe Acute Respiratory Syndrome Coronavirus Spike Protein: Implication for Vaccine Design
ABSTRACT The spike (S) glycoprotein of severe acute respiratory syndrome coronavirus (SARS-CoV) mediates the receptor interaction and immune recognition and is considered a majo...
Histone Acetyltransferases
▪ Abstract Transcriptional regulation in eukaryotes occurs within a chromatin setting and is strongly influenced by nucleosomal barriers imposed by histone proteins. Among the w...
Histone acetylation and an epigenetic code
The enzyme-catalyzed acetylation of the N-terminal tail domains of core histones provides a rich potential source of epigenetic information. This may be used both to mediate tra...
Somatic hypermutation in normal and transformed human B cells
Summary: In the human, most IgM + IgD + as well as CD5* peripheral blood B cells express unmutated V genes and thus can be assigned to a pre‐germinal centre (GC) stage of develo...
TGFβ attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells
Therapeutic antibodies that block the programmed death-1 (PD-1)–programmed death-ligand 1 (PD-L1) pathway can induce robust and durable responses in patients with various cancer...
Publication Info
- Year
- 1992
- Type
- article
- Volume
- 148
- Issue
- 5
- Pages
- 1561-1569
- Citations
- 176
- Access
- Closed
External Links
Social Impact
Altmetric
PlumX Metrics
Social media, news, blog, policy document mentions
Citation Metrics
176
OpenAlex
Cite This
Michele J. Losman,
Thomas M. Fasy,
Kristine E. Novick
et al.
(1992).
Monoclonal autoantibodies to subnucleosomes from a MRL/Mp(-)+/+ mouse. Oligoclonality of the antibody response and recognition of a determinant composed of histones H2A, H2B, and DNA..
The Journal of Immunology
, 148
(5)
, 1561-1569.
https://doi.org/10.4049/jimmunol.148.5.1561
Identifiers
- DOI
- 10.4049/jimmunol.148.5.1561