AbstractNZB and NZB/W mice have reduced anti‐sheep red cell (SRC) and 2,4,6‐trinitrophenyl‐plaque‐forming cell (TNP‐PFC) responses with age after injection of either the thymus‐dependent antigen TNP‐SRC or the thymus‐independent antigen TNP‐mouse red cells (MRC). However, the thymus‐dependent response diminished much faster than the thymus‐independent response. As a consequence, young New Zealand mice have a higher anti‐TNP response after injection of TNP‐SRC than after injection of TNP‐MRC, while old New Zealand mice have a higher anti‐TNP response after injection of TNP‐MRC than after injection of TNP‐SRC. The PFC avidity of NZB/W mice injected with TNP‐SRC diminished with age, while the PFC avidity of mice injected with TNP‐MRC did not change with age. Young NZB/W did not produce anti‐MRC‐PFC after being injected with either TNP‐MRC or TNP‐SRC. Old NZB/W mice had few spontaneous anti‐MRC‐PFC. The number of anti‐VRC PFC in old mice was increased 4 to 10 times after injection with either TNP‐SRC or TNP‐MRC.It is suggested that surveillance mechanisms are responsible for suppressing the autoimmune response to modified self‐antigens. The unregulated immune system of NZB and NZB/W mice appears to be an expression of the
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