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Objective: Rheumatoid arthritis (RA) is considered to be a prototypical autoimmune disorder. Several mechanisms have been proposed for the known pathologic function of B cells in RA, including antigen presentation, cytokine secretion, and humoral immunity. The aim of this study was to address the function of B lymphocytes in experimental arthritis. Methods: We mapped the adaptive immune response following collagen‐induced arthritis (CIA). We subsequently monitored these responses and disease outcomes in genetically modified mouse strains that lack mature B cell or germinal center (GC) functionality in a B cell–intrinsic manner. Results: Following primary immunization, the draining lymph nodes broadly reacted against type II collagen (CII) with the formation of GCs and T cell activation. Mice that lacked mature B cell function were fully protected against CIA and had a severely attenuated ability to mount isotype‐switched humoral immune responses against CII. Almost identical results were observed in mice that were selectively deficient in GC responses. Importantly, GC‐deficient mice were fully susceptible to collagen antibody–induced arthritis. Conclusion: We identified GC formation and anticollagen antibody production as the key pathogenic functions of B cells in CIA. The role of B cells in RA is likely to be more complex. However, targeting the GC reaction could allow for therapeutic interventions that are more refined than general B cell depletion. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the frequency of cell‐bound complement activation products (CB‐CAPs) as a marker of complement activation in patients with suspected systemic lupus erythematosus (SLE) and the usefulness of this biomarker as a predictor of the evolution of probable SLE into SLE as classified by the American College of Rheumatology (ACR) criteria. Methods: Patients in whom SLE was suspected by lupus experts and who fulfilled 3 ACR classification criteria for SLE (probable SLE) were enrolled, along with patients with established SLE as classified by both the ACR and the Systemic Lupus International Collaborating Clinics (SLICC) criteria, patients with primary Sjögren's syndrome (SS), and patients with other rheumatic diseases. Individual CB‐CAPs were measured by flow cytometry, and positivity rates were compared to those of commonly assessed biomarkers, including serum complement proteins (C3 and C4) and autoantibodies. The frequency of a positive multianalyte assay panel (MAP), which includes CB‐CAPs, was also evaluated. Probable SLE cases were followed up prospectively. Results: The 92 patients with probable SLE were diagnosed more recently than the 53 patients with established SLE, and their use of antirheumatic medications was lower. At the enrollment visit, more patients with probable SLE were positive for CB‐CAPs (28%) or MAP (40%) than had low complement levels (9%) (P = 0.0001 for each). In probable SLE, MAP scores of >0.8 at enrollment predicted fulfillment of a fourth ACR criterion within 18 months (hazard ratio 3.11, P < 0.01). Conclusion: Complement activation occurs in some patients with probable SLE and can be detected with higher frequency by evaluating CB‐CAPs and MAP than by assessing traditional serum complement protein levels. A MAP score above 0.8 predicts transition to classifiable SLE according to ACR criteria. [ABSTRACT FROM AUTHOR]