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

Abstract

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. 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. 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. 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.