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Accumulation of Antigen‐Driven Lymphoproliferations in Complement Receptor 2/ CD 21 −/low B Cells From Patients With Sjögren's Syndrome
Author(s) -
Glauzy Salomé,
Boccitto Marco,
Bannock Jason M.,
Delmotte Fabien R.,
Saadoun David,
Cacoub Patrice,
Ice John A.,
Sivils Kathy L.,
James Judith A.,
Wolin Sandra L.,
Meffre Eric
Publication year - 2018
Publication title -
arthritis and rheumatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.106
H-Index - 314
eISSN - 2326-5205
pISSN - 2326-5191
DOI - 10.1002/art.40352
Subject(s) - antigen , clone (java method) , cd19 , b cell , antibody , immunology , somatic hypermutation , polyclonal b cell response , biology , population , b cell receptor , naive b cell , microbiology and biotechnology , breakpoint cluster region , receptor , t cell , medicine , antigen presenting cell , immune system , dna , genetics , environmental health
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/ CD 21. 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 CD 21 −/low B cells isolated from the peripheral blood of 3 patients with SS . These lymphoproliferations expressed B cell receptors ( BCR s) 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 CD 21 −/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 CD 21 −/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.