Accumulation of Antigen-Driven Lymphoproliferations in Complement Receptor 2/CD21-/low B Cells From Patients With Sjögren's Syndrome

Arthritis Rheumatol. 2018 Feb;70(2):298-307. doi: 10.1002/art.40352. Epub 2018 Jan 18.

Abstract

Objective: Patients with Sjögren's syndrome (SS) are prone to develop malignant lymphomas, and a correlation has been established between the lymphoproliferations occurring in these disorders and the presence in patients' blood of an unusual B cell population that down-regulates complement receptor 2/CD21. This study was undertaken to identify the B cell compartment from which these lymphoproliferations emerge and determine the mechanisms that promote clonal B cell expansion in patients with SS.

Methods: The reactivity of antibodies expressed by CD19+CD10-CD27-IgM+CD21-/low cells isolated from the blood of patients with SS was tested using a polymerase chain reaction-based approach that allows us to clone and express, in vitro, recombinant antibodies produced by single B cells.

Results: Clonal expansions were identified in CD21-/low B cells isolated from the peripheral blood of 3 patients with SS. These lymphoproliferations expressed B cell receptors (BCRs) that displayed somatic hypermutation lineage trees characteristic of a strong selection by antigens; one of these antigens was identified as a ribosomal self antigen. When the mutated BCR sequences expressed by the expanded CD21-/low B cell clones from patients with SS were reverted in vitro to their germline counterparts, one clone remained autoreactive.

Conclusion: Clonal lymphoproliferations in patients with SS preferentially accumulate in the autoreactive CD21-/low B cell compartment often expanded in these subjects, and recognition of self antigens may drive the clonal B cell expansion while further refining BCR self-reactivity.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Autoantibodies / genetics
  • Autoantibodies / immunology
  • B-Lymphocytes / immunology*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Flow Cytometry
  • Fluorescent Antibody Technique, Indirect
  • Humans
  • Immunoprecipitation
  • Lymphoproliferative Disorders / etiology*
  • Lymphoproliferative Disorders / immunology
  • Middle Aged
  • Mutation
  • Polymerase Chain Reaction
  • Receptors, Antigen, B-Cell / immunology
  • Receptors, Antigen, B-Cell / metabolism
  • Receptors, Complement 3d / immunology
  • Receptors, Complement 3d / metabolism
  • Sjogren's Syndrome / complications
  • Sjogren's Syndrome / immunology*

Substances

  • Autoantibodies
  • Receptors, Antigen, B-Cell
  • Receptors, Complement 3d