Adaptive differentiation of murine lymphocytes. IV. (Responder × Nonresponder) F(1) T cells can be taught to preferentially help nonresponder,rather than responder, B cells

Abstract

Several years ago, we reported that T cells from (responder × nopresponder) F1 hybrids primed to the synthetic terpolymer, L-glutamic acid, L-lysine, L-tyrosine (GLT), 1 to which responses are governed by H-2-1inked Immune response-GLT genes, were restricted in their ability to provide GLT-specific help for 2,4-dinitrophenyl (DNP)-primed B cells from the respective parental mice in response to DNP-GLT (1). Thus, such F1 T cells were able to provide normal helper activity for DNP-specific B cells from responder, but not from nonresponder, donor mice. This finding contrasted sharply with the indiscriminant ability of F1 T cells to interact effectively with partner B cells from either parent when the carrier antigen employed was not one to which responses were governed by a known Ir gene. This observation has subsequently been confirmed by others in studies conducted in mice (2, 3) and guinea pigs (4).These observations were interpreted as an indication that in heterozygous individuals independent subpopulations of interacting T lymphocytes existed, one each corresponding to the respective parental type (1,5,6). Hence, we envisaged that stimulation of a (responder × nonresponder) F1 T-cell population by GLT would sensitize only the population of T cells able to recognize and react with the functional cell-interaction (CI) phenotype of the responder parent; F1 T cells corresponding to the nonresponder parent CI phenotype would not be stimulated by GLT. This situation would therefore be manifested as the defective ability of F1 T cells to interact with nonresponder B cells, irrespective of the antigen specificity of the latter. This original interpretation (1, 5, 6) has been reinforced by the subsequent demonstrations of the existence of independent Wl T-cell subpopulations that are reactive with each respective parental CI phenotype (7-12).

Cell-interaction molecules on immunocompetent lymphocytes. Development of anti-parent cell-interaction-molecule-receptor reactions in F1 hybrid mice and evidence for a unique F1 hybrid subset of interacting cells.

“…The rationale for initiating these studies stems from our belief that adaptive differentiation of lymphocytes, i.e., learning the appropriate self-recognition repertoire, is a dynamic, rather than a static, process by which immunocompetent cells perceive their environmental milieu and develop, accordingly, the cooperative phenotype dictated by that environment (1-5; reviewed in 6). Evidence in support of this notion previously reported from this laboratory includes: (a) the demonstration that the restricted phenotypes of helper T cells primed in situ in F~ --~ parent bone marrow chimeras or in neonatally tolerant parent environments are actually pseudo-restrictions resulting from some form of environmental restraint (7); and (b) the finding that it is possible to orchestrate the partner cell preferences of Fa lymphocytes primed to antigen under the influence of a parental cell-induced allogeneic effect such that the ultimate cooperating phenotypes displayed by such cells deviate in their preference for partner cells originating from one or the other parental type (8,9). Although direct evidence was lacking, we speculated that both environmental restraint and the ability to orchestrate the cooperating preferences of F~ hybrid lymphocytes were manifesta-tions of the development of responses against receptors for self cell-interaction (CI) 1 molecules that are requisite participants in cell-cell interactions (6)(7)(8)(9).…”

“…Evidence in support of this notion previously reported from this laboratory includes: (a) the demonstration that the restricted phenotypes of helper T cells primed in situ in F~ --~ parent bone marrow chimeras or in neonatally tolerant parent environments are actually pseudo-restrictions resulting from some form of environmental restraint (7); and (b) the finding that it is possible to orchestrate the partner cell preferences of Fa lymphocytes primed to antigen under the influence of a parental cell-induced allogeneic effect such that the ultimate cooperating phenotypes displayed by such cells deviate in their preference for partner cells originating from one or the other parental type (8,9). Although direct evidence was lacking, we speculated that both environmental restraint and the ability to orchestrate the cooperating preferences of F~ hybrid lymphocytes were manifesta-tions of the development of responses against receptors for self cell-interaction (CI) 1 molecules that are requisite participants in cell-cell interactions (6)(7)(8)(9). Such haplotypespecific anti-CI receptor responses would readily explain the permissiveness of the development of one subpopulation of self-recognizing cells (corresponding to one of the parental haplotypes) in the face of nonpermissiveness of the development of the self-recognizing cell subpopulation corresponding to the second haplotype involved.…”

Role of the major histocompatibility gene products in regulating the antibody response to dinitrophenylated poly(L-Glu55,L-Ala35,L-Phe9)n.

“…Recently, bone marrow irradiation chimeras have been used to probe the extent of the influence of the differentiating environment in restricting interactions of T cells with B cells of other MHC haplotypes. Although somewhat controversial, these studies suggested that the parental differentiating environment affected the collaborative phenotypic expression of a multipotential T cell repertoire (10,22,23).…”