Early requirement for B cells for development of spontaneous autoimmune thyroiditis in NOD.H-2h4 mice

B cells are known to play an important role in the pathogenesis of several autoimmune diseases. NOD.H-2h4 mice develop spontaneous autoimmune thyroidi tis (SAT) and anti-mouse thyroglobulin (MTg) autoantibodies, the levels of which correlate closely with the severity of thyroid lesions. NOD.H-2h4 mic e genetically deficient in B cells (NOD.K mu (null)) or rendered B cell-def icient by treatment from birth with anti-IgM develop minimal SAT. B cells w ere required some time in the first 4-6 wk after birth, because NOD.K mu (n ull) or NOD.H-2h4 mice did not develop SAT when they were reconstituted wit h B cells as adults, The requirement for B cells was apparently not solely to produce anti-MTg autoantibodies, because passive transfer of anti-MTg Ab did not enable B cell-deficient mice to develop SAT, and mice given B cell s as adults produced autoantibodies but did not develop SAT. B cell-deficie nt mice developed SAT if their T cells developed from bone marrow precursor s in the presence of B cells. Because B cells are required early in life an d their function cannot be replaced by anti-MTg autoantibodies, B cells may be required for the activation or selection of autoreactive T cells. These autoreactive T cells are apparently unable to respond to Ag if B cells are absent in the first 4-6 wk after birth.