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Patterns of ANA+ B cells for SLE patient stratification
Jolien Suurmond, … , Cynthia Aranow, Betty Diamond
Jolien Suurmond, … , Cynthia Aranow, Betty Diamond
Published May 2, 2019
Citation Information: JCI Insight. 2019;4(9):e127885. https://doi.org/10.1172/jci.insight.127885.
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Research Article Immunology

Patterns of ANA+ B cells for SLE patient stratification

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Abstract

IgG antinuclear antibodies (ANAs) are a dominant feature of several autoimmune diseases. We previously showed that systemic lupus erythematosus (SLE) is characterized by increased ANA+ IgG plasmablasts/plasma cells (PCs) through aberrant IgG PC differentiation rather than an antigen-specific tolerance defect. Here, we aimed to understand the differentiation pathways resulting in ANA+ IgG PCs in SLE patients. We demonstrate distinct profiles of ANA+ antigen-experienced B cells in SLE patients, characterized by either a high frequency of PCs or a high frequency of IgG+ memory B cells. This classification of SLE patients was unrelated to disease activity and remained stable over time in almost all patients, suggesting minimal influence of disease activity. A similar classification applies to antigen-specific B cell subsets in mice following primary immunization with T-independent and T-dependent antigens as well as in lupus-prone mouse models (MRL/lpr and NZB/W). We further show that, in both lupus-prone mice and SLE patients, the classification correlates with the serum autoantibody profile. In this study, we identified B cell phenotypes that we propose reflect an extrafollicular pathway for PC differentiation or a germinal center pathway, respectively. The classification we propose can be used to stratify patients for longitudinal studies and clinical trials.

Authors

Jolien Suurmond, Yemil Atisha-Fregoso, Ashley N. Barlev, Silvia A. Calderon, Meggan C. Mackay, Cynthia Aranow, Betty Diamond

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Figure 3

Frequencies of memory B cells and PCs upon primary immunization in mice.

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Frequencies of memory B cells and PCs upon primary immunization in mice....
(A) Model for differentiation of PCs. Two pathways can result in the differentiation of ANA+ IgG+ PCs, extrafollicular and germinal center, each leading to different proportions of IgG+ memory cells, IgM PCs, and IgG PCs. (B–G) C57BL/6 mice were immunized with NP-Ficoll or NP-CGG and analyzed at day 7, 14, and 21 after immunization. (B) Representative flow cytometry plots showing the frequency of NP+ cells among GC B cells, memory B cells, and PCs (the latter was analyzed upon cytoplasmic staining for NP). (C–F) Frequencies of NP+ GC B cells, NP+ memory B cells, NP+ IgM PCs, and NP+ IgG PCs. Each dot shows an individual mouse, and the bar represents the median. (G) Proportion of NP+ memory B cells and PCs These were calculated after subtracting the number of NP-specific cells in each population in unimmunized mice. Each pie chart shows the median for each strain (n = 4–6 mice per group). P values were calculated using χ2 test. ANA, antinuclear antibody; CGG, chicken γ globulin; FVD, fixable viability dye; GC, germinal center; NP, 4-hydroxy-3-nitrophenylacetyl; PC, plasmablast/plasma cell; SHM, somatic hypermutation.

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ISSN 2379-3708

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