Diversity, Cellular Origin and Autoreactivity of Antibody-secreting Cell Population Expansions in Acute Systemic Lupus Erythematosus

Overview

Journal Nat Immunol

Date 2015 May 26

PMID 26006014

Citations 286

Authors

Christopher M Tipton

Christopher F Fucile

Jaime Darce

Asiya Chida

Travis Ichikawa

Ivan Gregoretti

Sandra Schieferl

Jennifer Hom

Scott Jenks

Ron J Feldman

Ramit Mehr

Chungwen Wei

F Eun-Hyung Lee

Wan Cheung Cheung

Alexander F Rosenberg

Inaki Sanz

Affiliations

Soon will be listed here.

Abstract

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.

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