Immunopathologic role of B lymphocytes in rheumatoid arthritis: rationale of B cell-directed therapy.
Although the immunopathogenesis of rheumatoid arthritis (RA) remains unclear, recent advances have paved the way for new therapies, such as anti-cytokine and cell-directed therapies. Here, B cells have re-gained interest concerning the pathogenesis of a number of autoimmune diseases after observing that patients with RA and non-Hodgkin lymphoma, who received anti-CD20 therapy leading to B cell depletion, demonstrated remarkable improvements. The underlying modes of action appear to be related to B cell functions, such as deletion of memory B cells, interruption of immune activation, antigen-presentation and production of inflammatory cytokines. In many RA patients, synovial extrafollicular germinal centers develop, where B cells play an intimate role in local inflammation and the generation of memory B cells and plasma cells. These local processes lead to activation of the immune system and ultimately to joint destruction in RA. Recent data demonstrating the clinical value of B cell depletion in refractory RA patients substantiate the notion that B cells are important players in the pathogenesis of the disease. Future studies should clarify which functions are affected by B cell depletion, providing the promise of new avenues to patient-tailored therapies.
Martinez-Gamboa
Lorena
L
Charité Universitätsmedizin Berlin and German Centre for Rheumatic Research (DRFZ), Schumannstr. 20/21, 10098 Berlin, Germany.
Brezinschek
Hans-Peter
HP
Burmester
Gerd R
GR
Dörner
Thomas
T
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology*; D006801:Humans