Atypical VH-D-JH Rearrangements in Newborn Autoimmune MRL Mice

Klonowski, Kimberly D.; Primiano, Laura L.; Monestier, Marc

doi:10.4049/jimmunol.162.3.1566

Cited by 54 publications

(1 citation statement)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…6E ). These results suggest that CD138 int B cells may be autoreactive B cells, as BCRs with long CDR3 sequences tend to be autoreactive ( 2 31 ). Class-switched CD138 int B cells appeared to be derived from extrafollicular B cell responses of unswitched CD138 int B cells since they do not accumulate high levels of somatic mutations.…”

Section: Resultsmentioning

confidence: 86%

Low-Level Expression of CD138 Marks Naturally Arising Anergic B Cells

et al. 2022

View full text Add to dashboard Cite

Autoreactive B cells are not entirely deleted, but some remain as immunocompetent or anergic B cells. Although the persistence of autoreactive B cells as anergic cells has been shown in transgenic mouse models with the expression of B cell receptor (BCR) reactive to engineered self-antigen, the characterization of naturally occurring anergic B cells is important to identify them and understand their contribution to immune regulation or autoimmune diseases. We report here that a low-level expression of CD138 in the splenic B cells marks naturally arising anergic B cells, not plasma cells. The CD138 int B cells consisted of IgM low IgD high follicular (FO) B cells and transitional 3 B cells in homeostatic conditions. The CD138 int FO B cells showed an anergic gene expression profile shared with that of monoclonal anergic B cells expressing engineered BCRs and the gene expression profile was different from those of plasma cells, age-associated B cells, or germinal center B cells. The anergic state of the CD138 int FO B cells was confirmed by attenuated Ca 2+ response and failure to upregulate CD69 upon BCR engagement with anti-IgM, anti-IgD, anti-Igκ, or anti-IgG. The BCR repertoire of the CD138 int FO B cells was distinct from that of the CD138 − FO B cells and included some class-switched B cells with low-level somatic mutations. These findings demonstrate the presence of polyclonal anergic B cells in the normal mice that are characterized by low-level expression of CD138, IgM downregulation, reduced Ca 2+ and CD69 responses upon BCR engagement, and distinct BCR repertoire.

show abstract

Section: Resultsmentioning

confidence: 86%

Low-Level Expression of CD138 Marks Naturally Arising Anergic B Cells

et al. 2022

View full text Add to dashboard Cite

show abstract

Defective Early B Cell Tolerance Checkpoints in Patients With Systemic Sclerosis Allow the Production of Self Antigen–Specific Clones

Glauzy

Olson

May

et al. 2021

Arthritis & Rheumatology

View full text Add to dashboard Cite

Objective. Early selection steps preventing autoreactive naive B cell production are often impaired in patients with autoimmune diseases, but central and peripheral B cell tolerance checkpoints have not been assessed in patients with systemic sclerosis (SSc). This study was undertaken to characterize early B cell tolerance checkpoints in patients with SSc.Methods. Using an in vitro polymerase chain reaction-based approach that allows the expression of recombinant antibodies cloned from single B cells, we tested the reactivity of antibodies expressed by 212 CD19+CD21 low CD10+IgM high CD27À new emigrant/transitional B cells and 190 CD19+CD21+CD10ÀIgM+CD27À mature naive B cells from 10 patients with SSc.Results. Compared to serum from healthy donors, serum from patients with SSc displayed elevated proportions of polyreactive and antinuclear-reactive new emigrant/transitional B cells that recognize topoisomerase I, suggesting that defective central B cell tolerance contributes to the production of serum autoantibodies characteristic of the disease. Frequencies of autoreactive mature naive B cells were also significantly increased in SSc patients compared to healthy donors, thus indicating that a peripheral B cell tolerance checkpoint may be impaired in SSc.Conclusion. Defective counterselection of developing autoreactive naive B cells in SSc leads to the production of self antigen-specific B cells that may secrete autoantibodies and allow the formation of immune complexes, which promote fibrosis in SSc.

show abstract

NGS-Based B-Cell Receptor Repertoire AnalysisRepertoire analyses in the Context of Inborn Errors of Immunity

Schouwenburg

Burg

IJspeert

2022

Methods in Molecular Biology

View full text Add to dashboard Cite

Inborn errors of immunity (IEI) are genetic defects that can affect both the innate and the adaptive immune system. Patients with IEI usually present with recurrent infections, but many also suffer from immune dysregulation, autoimmunity, and malignancies.Inborn errors of the immune system can cause defects in the development and selection of the B-cell receptor (BCR) repertoire. Patients with IEI can have a defect in one of the key processes of immune repertoire formation like V(D)J recombination, somatic hypermutation (SHM), class switch recombination (CSR), or (pre-)BCR signalling and proliferation. However, also other genetic defects can lead to quantitative and qualitative differences in the immune repertoire.In this chapter, we will give an overview of protocols that can be used to study the immune repertoire in patients with IEI, provide considerations to take into account before setting up experiments, and discuss analysis of the immune repertoire data using Antigen Receptor Galaxy (ARGalaxy).

show abstract

Atypical VH-D-JH Rearrangements in Newborn Autoimmune MRL Mice

Cited by 54 publications

References 49 publications

Low-Level Expression of CD138 Marks Naturally Arising Anergic B Cells

Low-Level Expression of CD138 Marks Naturally Arising Anergic B Cells

Defective Early B Cell Tolerance Checkpoints in Patients With Systemic Sclerosis Allow the Production of Self Antigen–Specific Clones

NGS-Based B-Cell Receptor Repertoire AnalysisRepertoire analyses in the Context of Inborn Errors of Immunity

Contact Info

Product

Resources

About