Arthritogenic monoclonal antibodies from K/BxN mice.

MACCIONI M, ZEDER-LUTZ G, HUANG H, EBEL C, GERBER P, HERGUEUX J, MARCHAL P, DUCHATELLE V, DEGOTT C, VAN REGENMORTEL M, BENOIST C, MATHIS D.

ROCKEFELLER UNIV PRESS

Año: 2002 p. 1071 - 1071

rthritis in the K/BxN mouse model is provoked by pathogenic antibodies (Abs) directed against a ubiquitously expressed protein, glucose-6-phosphate isomerase (GPI). To begin dissecting the repertoire of arthritogenic immunoglobulins (Igs) in the K/BxN model, and to provide a basis for comparison with RA patients we have generated anti-GPI monoclonal Abs (mAbs) from spontaneously activated B cells in the lymphoid organs of arthritic mice. B cell clones with anti-GPI specificities were present at extraordinarily high frequencies in the spleen, and less frequently in other lymphoid organs and in the synovial fluid. None of the anti-GPI mAbs induced arthritis when injected individually into healthy recipients, but most were effective when combined in pairs or larger pools. Arthritogenic combinations depended on mAbs of the IgG1 isotype, which bound to GPI with Kd in the 10(-9) M range, with no indication of cooperative binding between complementing pairs. Pathogenicity was not associated