B cell depletion reduces the number of autoreactive T helper cells and prevents glucose-6-phosphate isomerase-induced arthritis.

B cell depletion reduces the number of autoreactive T helper cells and prevents glucose-6-phosphate isomerase-induced arthritis.

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The therapeutic benefit of B cell depletion in patients with rheumatoid arthritis has provided proof of concept that B cells are relevant for the pathogenesis of arthritis.It remains unknown which B cell effector functions contribute to the induction or chronification of arthritis.We studied the clinical and immunological effects of B cell depletion in glucose-6-phosphate isomerase-induced arthritis.We targeted CD22 to deplete B cells.

Mice were depleted of B cells before or after immunization with glucose-6-phosphate isomerase (G6PI).The clinical and histological effects were studied.G6PI-specific antibody Charms (Jewelry) responses were measured by ELISA.G6PI-specific T helper (Th) cell responses were assayed by polychromatic flow cytometry.

B cell depletion prior to G6PI-immunization prevented arthritis.B cell depletion after immunization ameliorated arthritis, whereas B cell depletion in arthritic mice was ineffective.Transfer of antibodies from arthritic mice into B cell depleted recipients did not reconstitute arthritis.B cell depleted mice harbored Foot Rests much fewer G6PI-specific Th cells than control animals.

B cell depletion prevents but does not cure G6PI-induced arthritis.Arthritis prevention upon B cell depletion is associated with a drastic reduction in the number of G6PI-specific effector Th cells.