Accumulation of Antigen‐Driven Lymphoproliferations in Complement Receptor 2/CD21−/low B Cells From Patients With Sjögren's Syndrome
2018
Objective
Sjogren's Syndrome (SS) patients are prone to develop malignant lymphomas and a correlation has been established between lymphoproliferations and the presence in patients’ blood of an unusual B cell population that downregulated complement receptor 2/CD21. We sought to determine from which B cell compartment lymphoproliferations in SS patients emerge and what are the mechanisms that promote these clonal B cell expansions.
Methods
Using a PCR-based approach that allows us to clone and express, in vitro, recombinant antibodies produced by single B cells, we tested the reactivity of antibodies expressed by CD19+CD10-CD27-IgM+CD21-/low cells from SS patients.
Results
We identified clonal expansions in CD21-/low B cells isolated from the blood of three SS patients. All three lymphoproliferations expressed B cell receptors (BCRs) that displayed somatic hypermutation lineage trees characteristic of strong selection by antigens, one of which was identified as a ribosomal self-antigen. When mutated BCR sequences expressed by SS expanded clones were reverted, in vitro, to their germline counterparts, one remained autoreactive.
Conclusion
Clonal lymphoproliferations in SS patients preferentially accumulate in the autoreactive CD21-/low B cell compartment, which is often amplified in these subjects, and (self)-antigen recognition may drive expansion while further refining BCR (self)-reactivity.
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