The effect of activating and inhibiting Fc-receptors on murine mercury-induced autoimmunity.

• Fc-receptors for IgG (Fc gamma R) link cellular and humoral immune responses, controlling the balance between activating and inhibitory immune responses, and are involved in autoimmune diseases. Mercury (Hg) induces an autoimmune condition in genetically (H-2(s,q,f)) susceptible mice characterized by lymphoproliferation, hypergammaglobulinemia and IgG antinucleolar antibodies (ANoA). Here we investigate the role of activating (Fc gamma RI, Fc gamma RIII) and inhibitory (Fc gamma RIIb) Fc-receptors on mercury-induced autoimmunity (HgIA) using DBA/1 mice (H-2(q))(-) with targeted Fc gamma R mutations and wild type (wt) mice. Mice deficient for the FcR gamma-chain or FcyRIII and treated with 15 mg/L HgCl2 showed a delayed and attenuated IgG1, IgG2a and IgG2b ANoA response compared to wt mice. Female Hg-treated FcyRIIB(-/-) mice showed a significant increased of lgG2b ANoA development compared to wt mice. The total serum IgG1 response due to Hg was attenuated in FcR gamma(-/-) and Fe gamma RIII-/- mice compared to wt mice. Hg-treated Fc gamma RIIB-/- mice showed an increase of both serum IgG1 and IgE compared to wt mice. We conclude that FcyRIII is of importance for the rapidity and final strength of the ANoA response and the increase in serum IgG1 in HgIA, while lack of Fc gamma RIIb increases the IgG2b ANoA response and the serum IgG1 and IgE response.

Ämnesord

NATURVETENSKAP  -- Biologi (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences (hsv//eng)

Nyckelord

Mercury

Fc gamma R

autoimmunity

mice

ANoA

Biology

Biologi

MEDICINE

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