REACTIVITY OF LYMPItOCYTES FROM CONVENTIONAL AND GERMFREE RATS TO ALLOGENEIC AND XENOGENEIC CELL SURFACE ANTIGENS* BY DARCY B. WILSON,$ PH.D., AXrD

The proportion of lymphocytes present in an individual which are reactive to the major histocompatibility (H) 1 alloantigens of another member of the same species (histocompatibility antigen-reactive cells [H-ARC]) has been shown to be unusually large. Estimates derived from studies with the graft-versus-host (GVH) reaction in vivo (1-4) and with the mixed lymphocyte interaction (MLI) in vitro (5, 6) are in substantial agreement, and place this number at approximately 2-4% of the cells of the circulating lymphocyte pool. This conclusion is difficult to accept in view of the constraints of the clonal selection hypothesis and consequently, various alternatives of a general nature have been proposed to account for these findings (7, 8). These include the possibilities that the large proportion of H-ARC (a) involve a large number which are "recruited" or nonspecifically activated; (b) are multipotential, having the capacity to react to any one of a series of different antigen determinants including other H alloantigens; (c) represent the cumulative activity of a great many subpopulations of antigen-reactive lymphocytes, each present in low frequency and stimulated to proliferate by a very large number of antigenic differences which might exist between two individuals; (d) reflect the existence of a prior state of immunization in the cell donors to cross-reactive dietary and environmental antigens, or to altered surface specificities on somatic cells such as tumor-specific antigens on spontaneously arising and successfully suppressed neoplasms; (e) have a low stimulation threshold and are triggered to respond as a consequence of multivalent binding to low affinity receptor sites by antigenic determinants represented in high density on cellular membranes; or (f) represent a pool of antigen-reactive cells important in some not yet defined crucial step(s) of ontogeny and their high frequency is brought about by some unknown expansion mechanism under innate genetic control (i.e., Jerne's recent model [9]).