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In the previous paper we showed that the immune response to sheep red cells (SRBC) was degenerate; serum antibodies showed increasing loss of specificity, signalled by cross-reactions with horse RBC (HRBC), with time after immunization and with hyperimmunization. In the present report we have analysed the role T cells may play in this process. To do this we studied the antibodies made by mice deprived of T cells by irradiation as well as those made by normal mice immunized with SRBC in distilled water, which was shown to depress the DNA synthetic response of T cells. In both instances the mice with fewer responding T cells made less antibody which could agglutinate HRBC than did the appropriate controls. This was true even when no difference in anti-SRBC titre was apparent. In addition we showed that the antibody made by mice with reduced numbers of T cells was less effective at passive suppression of the immune response to SRBC than was similarly titred (against SRBC) antibody made by normal mice. Thus, certain sub-populations of antibodies, normally made in response to SRBC, immunization, are particularly thymus dependent. We have discussed why we think they are those of particularly high affinity. [ABSTRACT FROM AUTHOR]

We found that some mice immunized with sheep red blood cells (SRBC) made antibodies that agglutinated horse RBC (HRBC). Absorption studies indicated that the cross-reacting antibodies were highly avid. They appeared either late in a primary response, in secondary responses, or after multiple immunizations. Thus, the antibody response to SRBC loses specificity with time and is a further example of the degeneracy of the immune response. The similarities between the system we described and previously studied examples of degeneracy suggest that their bases may be the same; reactions of high affinity antibodies with related determinants. This interpretation was strengthened by the observation that antibodies made by mice which had recently escaped from tolerance were particularly deficient in cross-reacting subsets. The possible pitfalls of using hyperimmune serum in tests requiring high degrees of immunological specificity were emphasized. [ABSTRACT FROM AUTHOR]

Previous studies have shown that thymectomized lethally irradiated bone marrow grafted mice, reconstituted with thymocytes and pretreated with a large dose of sheep red blood cells (SRBC), are unable to respond to a subsequent immunizing injection of SRBC even after an inoculation of normal thymocytes. If, however, the mice are not thymocyte reconstituted prior to the pretreatment with SRBC, they can respond almost normally to an immunizing injection of SRBC if inoculated with normal thymocytes after the termination of antigen pretreatment. In the present study the immunosuppressive effect of the presence of thymocytes during the antigen pretreatrnent was studied by adoptively transferring the spleen cells of the antigen pretreated mice to thymus-deprived chimeras. These spleen cells not only did not co-operate with normal thymocytes in the secondary hosts, but they also prevented the co-operation of normal thymocytes with normal bone marrow derived cells. Untreated spleen cells or treated spleen cells from mice not reconstituted with thymocytes did not affect cell co-operation in the secondary hosts. The abrogation of the co-operation in the secondary host was specific in that the addition of spleen cells did not affect the anti-horse red blood cell response, if the primary host made antibody as a result of the pretreatment, the transfer of their spleen cells did not prevent antibody production in the secondary host. [ABSTRACT FROM AUTHOR]