A subset of antibodies targeting citrullinated proteins confers protection from rheumatoid arthritis.

Although elevated levels of anti-citrullinated protein antibodies (ACPAs) are a hallmark of rheumatoid arthritis (RA), the in vivo functions of these antibodies remain unclear. Here, we have expressed monoclonal ACPAs derived from patients with RA, and analyzed their functions in mice, as well as their specificities. None of the ACPAs showed arthritogenicity nor induced pain-associated behavior in mice.

Lymphoma-associated mutations in autoreactive memory B cells of patients with Sjögren's syndrome.

We recently demonstrated that normal memory B lymphocytes carry a substantial number of de novo mutations in the genome. Here, we performed exome-wide somatic mutation analyses of bona fide autoreactive rheumatoid factor (RF)-expressing memory B cells retrieved from patients with Sjӧgren's syndrome (SS). The amount and repertoire of the de novo exome mutations of RF B cells were found to be essentially different from those detected in healthy donor memory B cells.

Absence of Epstein-Barr virus DNA in anti-citrullinated protein antibody-expressing B cells of patients with rheumatoid arthritis.

Objective: Rheumatoid arthritis (RA) is characterized by the presence of disease-specific autoreactive B cell responses, in particular those generating anti-citrullinated protein antibodies (ACPA). For many years, Epstein-Barr virus (EBV) has been implicated in disease pathogenesis, possibly by facilitating the development and persistence of autoreactive B cells. To test this hypothesis, the presence of EBV episomes in ACPA-expressing B cells was analyzed.

Benchmarking computational methods for B-cell receptor reconstruction from single-cell RNA-seq data.

Multiple methods have recently been developed to reconstruct full-length B-cell receptors (BCRs) from single-cell RNA sequencing (scRNA-seq) data. This need emerged from the expansion of scRNA-seq techniques, the increasing interest in antibody-based drug development and the importance of BCR repertoire changes in cancer and autoimmune disease progression. However, a comprehensive assessment of performance-influencing factors such as the sequencing depth, read length or number of somatic hypermutations (SHMs) as well as guidance regarding the choice of methodology is still lacking.