Regulators of B-cell activity in SLE: a better target for treatment than B-cell depletion?
B cells, being a source of characteristic antinuclear autoantibodies, play a crucial role in the pathogenesis of systemic lupus erythematosus (SLE). Evidences indicate that alterations in B-cell regulation are responsible for B-cell hyperactivity as seen in SLE. T cells, soluble factors, and even B cells themselves regulate effector B-cell functions. The latter, so-called regulatory B cells possess regulatory function through production of the cytokine interleukin-10 (IL-10) that can damp down the humoral immune responses. This review will focus on B-cell regulation in the pathogenesis of SLE as a target for intervention. In particular, the regulatory impact of T cells through costimulation, soluble factors such as B lymphocyte stimulator, and the characteristics of IL 10-producing regulatory B cells will be discussed. Therapies targeting B cells as well as B-cell regulation seem promising, but the precise mechanisms involved in these interventions are not completely understood. More insight into B-cell regulation in SLE, and particularly in regulatory B cells, could lead to novel therapeutic strategies.
Department of Rheumatology, University Medical Center Groningen, Groningen, The Netherlands.
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S
Dolff
W H
WH
Abdulahad
M
M
Bijl
C G M
CG
Kallenberg
D000974:Antibodies, Antinuclear / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology / Q000502:physiology*; D002450:Cell Communication / Q000276:immunology / Q000502:physiology; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000276:immunology / Q000503:physiopathology / Q000628:therapy*; D008212:Lymphocyte Depletion; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology
D000974:Antibodies, Antinuclear; D016753:Interleukin-10