PMID: 8612199Nov 1, 1995Paper

VH3-21 B cells escape from a state of tolerance in rheumatoid arthritis and secrete rheumatoid factor

Molecular Medicine
X HeC M Weyand

Abstract

Rheumatoid factor (RF) is a characteristic but not pathognomic feature in patients with rheumatoid arthritis (RA). It is unknown whether the repertoire of immunoglobulin genes utilized by RF+ B cells of RA patients is unique and whether RF+ B cells in normal individuals are silenced or deleted. Clonal B cell populations were established from the peripheral blood of normal donors (127 B cell clones), RA patients (113 RF- and 60 RF+ B cell clones) and patients with primary Sjögren's syndrome (82 RF- and 47 RF+ B cell clones) by coculturing with anti-CD3-stimulated T helper cell clones. The cross-reactivity pattern of antibodies secreted by the B cell clones was determined by ELISA on a panel of antigens. The molecular structure of the IgM heavy chains was characterized by VH family-specific RT-PCR and sequencing. VH elements which correlated with RF specificity were identified. The responsiveness of B cells expressing these VH elements to T helper cell signals was compared in normal individuals and RA patients. The majority of RF+ B cells were monospecific when specificity was tested on five antigens. RF+ B cells expressed a significantly different repertoire of VH gene segments than RF- B cells. In particular, the VH3 gene segme...Continue Reading

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