Severe combined immunodeficient (SCID) mice: a model for investigating human thyroid autoantibody synthesis

SUMMARY We have studied the ability of lymphocytes from the blood, thyroid and lymph nodes of patients with autoimmune thyroid disease (AITD) to produce auloantibodies to thyroglobulin (Tg) and/or thyroid peroxidasc (TPO) in SCID mice. Human IgG class Tg and/or TPO antibodies were detectable in plasma from SCID mice 7 days after transfer of 15–25 × I06 cells mouse and the highest levels were recorded 2–3 weeks later. In contrast, Tg and/or TPO antibodies were undctcctablc in recipients of lymphocytes from thyroid antibody negative controls. AITD thyroid lymphocytes produced the most antibody in recipient mice and lower levels were observed in recipients of AITD blood and lymph node lymphocytes. The amounts of Tg and or TPO antibody detected were in accordance with the ability of thyroid and lymph node lymphocytes to secrete these autoantibodies spontaneously in culture (indicating the presence of cells activated in the patient) and with the capacity of blood lymphocytes (probably B memory cells) to secrete Tg and or TPO antibodies in culture in response to pokeweed mitogen. Tg antibodies in plasma from SCTD recipients of thyroid lymphocytes were of subclasses IgG1, IgG2 and IgG4 and the proportions closely resembled those of the donor's scrum Tg antibodies. Blood lymphocytes transferred to SCiD recipients were also able to produce Tg antibodies of subclasses1, 2 and 4 but the subclass distribution varied between mice and the reason for this is not clear at present. Since SCID mice provide an environment in which B lymphocytes from patients with AITD can be activated without mitogen to secrete thyroid antibodies, this model will provide a powerful system for elucidating the mechanisms regulating the secretion of human antibodies to Tg and TPO.