Deficiency of the inhibitory Fc gamma RIIB renders mice susceptible to autoimmune disorders characterized with cellular infiltration of target tissue. To analyze the role of Fc gamma RIIB in an antibody-mediated autoimmune disease, experimental autoimmune myasthenia gravis (EAMG), Fc gamma RIIB knockout (KO) and wild-type mice were immunized with acetylcholine receptor (AChR). In contrast with previous reports, Fc gamma RIIB KO mice were mildly resistant to EAMG despite preserved anti-AChR antibody production and neuromuscular junction complement deposition capacity. EAMG resistance was associated with reduced lymph node cell IL-6 and IL-10 production and increased CD4(+)CD25(+) cell ratios in lymph nodes. Our data suggest that Fc gamma RIIB promotes antibody-mediated autoimmunity. (C) 2008 Elsevier B.V. All rights reserved.