Internalization of anti-Hu IgG is not Fc gamma receptor mediated

Patients with paraneoplastic subacute sensory neuronopathy or encephalomyelitis associated with small cell lung cancer cells (SCLC) frequently harbor anti-Hu antibodies (also called antineuronal nuclear antibodies type 1) in serum and CSF. ^[1] These antibodies react with a family of nuclear proteins, with apparent molecular mass ranging from 35 to 45 kD, expressed in neurons and SCLC cells. ^[2] Anti-Hu antibodies are one example of ANA associated with autoimmune disease. ANA occur in a variety of autoimmune disorders, most classically systemic lupus erythematosus. The ability of these antibodies to interact with nuclear antigens in living cells has been questioned and the relevance of the antibodies to disease production doubted. However, several groups have demonstrated that autoantibodies can penetrate living cells. ^[3]

Anti-Hu IgG penetrates viable Hu-positive SCLC cells and localizes in the nucleus. ^[4] How this IgG internalizes into the cell and translocates to the nucleus is unknown. Immunocytochemistry, immunoprecipitation, and flow cytometry show no Hu antigen on the cell surface (Lieberman and Hormigo, unpublished data; Posner, personal communication). Alternatively, internalization may be mediated by receptors that recognize the Fc portion of immunoglobulin molecules, the Fc gamma receptors (Fc gamma Rs). Fc gamma Rs comprise a family of molecules within the immunoglobulin superfamily. There are three main classes: Fc gamma RI, Fc gamma RII, and Fc gamma RIII. ^[5] For example, the internalization of …