Diversity, cellular origin and autoreactivity of antibody-secreting cell population expansions in acute systemic lupus erythematosus.
Christopher M TiptonChristopher F FucileJaime DarceAsiya ChidaTravis IchikawaIvan GregorettiSandra SchieferlJennifer HomScott JenksRon J FeldmanRamit MehrChungwen WeiF Eun-Hyung LeeWan Cheung CheungAlexander F RosenbergIñaki SanzPublished in: Nature immunology (2015)
Acute systemic lupus erythematosus (SLE) courses with surges of antibody-secreting cells (ASCs) whose origin, diversity and contribution to serum autoantibodies remain unknown. Here, deep sequencing, proteomic profiling of autoantibodies and single-cell analysis demonstrated highly diversified ASCs punctuated by clones expressing the variable heavy-chain region VH4-34 that produced dominant serum autoantibodies. A fraction of ASC clones contained autoantibodies without mutation, a finding consistent with differentiation outside the germinal centers. A substantial ASC segment was derived from a distinct subset of newly activated naive cells of considerable clonality that persisted in the circulation for several months. Thus, selection of SLE autoreactivities occurred during polyclonal activation, with prolonged recruitment of recently activated naive B cells. Our findings shed light on the pathogenesis of SLE, help explain the benefit of agents that target B cells and should facilitate the design of future therapies.
Keyphrases
- systemic lupus erythematosus
- single cell
- disease activity
- induced apoptosis
- rna seq
- liver failure
- cell cycle arrest
- respiratory failure
- hiv infected
- endoplasmic reticulum stress
- nlrp inflammasome
- cell death
- high throughput
- drug induced
- mesenchymal stem cells
- stem cells
- rheumatoid arthritis
- aortic dissection
- cell therapy
- bone marrow
- acute respiratory distress syndrome