The immune response to homologous lens crystallin. I. Antibody production after lens injury.

Using a sensitive radioimmunoassay to homologous mouse alpha-crystallin, it was established that autoantibodies are produced to this self constituent in mice after rupture of the lens capsule by needling. Antibody to lens crystallin was detected within 4 days of lens rupture and persisted for 24 days, suggesting that these mice are not tolerant to alpha-crystallin at the B cell level. However, T cells from mice immunized with homologous crystallin cannot be stimulated to proliferate by either homologous or heterologous crystallin. On the other hand, lymphocytes from mice immunized with bovine alpha-crystallin can be stimulated to proliferate to bovine crystallin, but not to either unfractionated mouse crystallin (MC) or purified mouse alpha-crystallin. At the level of detection, therefore, T cells appear to be tolerant to homologous alpha-crystallin, but not to heterologous alpha-crystallin. LPS resulting from bacterial contamination after needling was ruled out as a necessity for antibody production because antibody to mouse alpha-crystallin was produced after sterile lens rupture with a laser. However, LPS and poly A:U did enhance the antibody response to alpha-crystallin. These data suggest that T cells, but not B cells, are tolerant to homologous crystallin and that antibody results from circumvention of specific helper T cell requirements for antibody synthesis. The implications of these findings for tolerance and autoimmune uveitis are discussed.