Adaptive differentiation of murine lymphocytes. II. The thymic microenvironment does not restrict the cooperative partner cell preference of helper T cells differentiating in F1 leads to F1 thymic chimeras.

Abstract

This study was conducted to analyze the extent to which the major histocompatibility complex (MHC) a genotype of the thymus restricts the cooperating phenotype of helper T cells with respect to their ultimate ability to interact effectively with partner B lymphocytes in the development of antibody responses. These studies, like others reported previously (I, 2), made use of artificially constructed bone marrow chimeras prepared by reconstituting aduh-thymectomized, lethally irradiated F1 mice with syngeneic F1 bone marrow, together with transplanted thymuses from either F1 or parental donors. Reconstituted mice of these types were then immunized with keyhole limpet hemocyanin (KLH) and their KLH-specific helper T cells so induced were tested for the cooperative helper activity they could provide to 2,4-dinitrophenyl (DNP)-primed B lymphocytes derived from conventional F1 or parental donors in developing secondary anti-DNP antibody responses to DNP-KLH. The results clearly show that the thymus influences little, and certainly does not restrict, the partner cell preference displayed by helper T cells differentiating in such environments. Moreover, the extent of thymic influence differed depending on the class of antibody being produced with the help of such cells.This investigation is an extension of earlier studies in this (3) and other laboratories (4-10) which have addressed the predictions of the concept of adaptive differentiation (3,(11)(12)(13)(14). This notion ascribes the partner cell preferences of various cells of the lymphoid system, known to be genetically controlled by various regions of the MHC (15), to processes of selection that occur early during cell differentiation and which are determined by the MHC phenotype of the environment in which such differentiation occurs (3,(11)(12)(13)(14). The first experiments supporting this concept were performed * Publication 94 from the Department of Cellular and Developmental Immunology and publication

Antigen recognition. V. Requirement for histocompatibility between antigen-presenting cell and B cell in the response to a thymus-dependent antigen, and lack of allogeneic restriction between T and B cells.

“…Katz has, however, recently reported that the H-2 restriction of T cells from parent---~Fx chimeras is considerably less tight than was previously thought and that the "pseudorestriction" seen for cells primed in situ in the chimeric environment can be overcome by adoptive priming in the context of appropriate APC. This and other results (25)(26)(27)(28) have suggested that the original interpretation of the data suggesting adaptive differentiation was overly stringent and that the true situation may be more one of "environmental restraint," in which extrathymic influences during differentiation may be of critical importance. Sprent (8), using in vivo positive selection to antigen of F1 cells in a parental environment, found that H-2 restriction was imposed during the selection process, a result not compatible with ours.…”

Humoral and cell-mediated immune responses in fully allogeneic bone marrow chimera in mice

“…Thus, it would appear that although some degree of aliogeneic preference or restriction in indirect PFC response may be obtained in these chimeric mice, it is not as limiting with respect to secondary T-dependent antibody responses as might be extrapolated from the existing literature (1-3, 5, 6, 11-13, 37-39). It seems to us that these findings are (44), which suggest that the restrictions are not absolutely binding if there is opportunity for prior experience and a period for learning.…”

Incomplete Tolerance to MHC Antigens in Irradiation Chimeras: Implications for MHC Restriction and Self Tolerance

“…Contradictory evidence also exists concerning the R antigen specificity of T cells that mediate delayed hypersentitivity or helper effects (Miller et al 1979, Smith & Miller 1980, Sprent 1978, Katz et al 1979. It seems likely that their development pathway shares common features with Tc cells, although their R antigens are determined by the / region of the murine H-2 gene complex instead of the K and D regions relevant to Tc cell recognition.…”