Adaptive differentiation of murine lymphocytes. I. Both T and B lymphocytes differentiating in F1 transplanted to parental chimeras manifest preferential cooperative activity for partner lymphocytes derived from the same parental type corresponding to the chimeric host.

Abstract

Approximately 5 yr ago the first observations that documented genetic restrictions imposed by genes within the major histocompatibility complex (MHC) 1 upon cooperative interactions between T lymphocytes and macrophages and between T lymphocytes and B lymphocytes were described (1-3). Later, it was found that the most efficient lysis of target cells by specific cytotoxic T lymphocytes (CTL) occurred when the CTL and target cell, respectively, shared gene identities in the mouse H-2 complex (4-8). Genetic mapping studies documented that gene(s) controlling T-B-cell interactions are located in the/-region of the mouse 1-1-2 complex (9), whereas those involved in CTL-target interactions are located in the K and D regions of/_/. 2 (10, 11).The subject of MHC-linked genetic restrictions on cell-cell communication processes has evoked controversy both in terms of the extent of such constraints on cell-cell interactions and on the best possible interpretations of such restrictions (12-14). Essentially two major concepts have evolved to explain these genetic restrictions on cell interactions. The first hypothesis, which stemmed from analysis of such restrictions in T-B-cell interactions, considered that interactions among various cell types in the immune system are mediated by cell interaction (CI) molecules located on the cell surface, at least some of which are encoded by MHC genes (i.e./-region genes in this case), and which are quite distinct from the lymphocyte receptors specific for conventional antigens (13-15). The CI molecule concept therefore emphasizes a dual recognition mechanism which involves at least two distinct molecular interactions in lymphocyte activation, one utilizing antigen-specific receptors and the second consisting of reactions between the relevant CI structures and their corresponding receptors. The second major concept, derived primarily from studies in the CTL systems, considered that T lymphocytes have receptors which recognize not antigen alone, but antigen in some form of association with MHC gene products on cell surface membranes; this concept of "ahered-setf" (16) recognition by T lymphocytes differs substantially from the CI molecule concept in predicting the existence of a single receptor on T cells simultaneously recognizing modified determinants on the cell surface. To date, no definitive proof has been obtained to establish which of these two models is correct.

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.

“…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).…”

“…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…”

“…The proteins, reagents, and preparation of hapten-protein conjugates were the same as those described in earlier reports (3,16). 9 tool of DNP/100,000 dahons of KLH (DNP9-KLH) and 2.1 × 10 -~ tool of DNP/mg of Ascaris suum (DNP2.x-ASC) were employed in these studies.…”

“…9 tool of DNP/100,000 dahons of KLH (DNP9-KLH) and 2.1 × 10 -~ tool of DNP/mg of Ascaris suum (DNP2.x-ASC) were employed in these studies. The preparation of anti-0 serum, its characterization and method of anti-0 serum treatment of spleen cells, determination of serum anti-DNP antibody levels by radioimmunoassay, and the method for enumerating DNP-specific plaque-forming cells (PFC) of the IgG class are described elsewhere (3,(16)(17)(18).…”

“…More recently, several investigators, including ourselves, have conducted such experiments using various types of bone marrow chimeras and analyzing the cells differentiating in such environments for either cytotoxic T-lymphocyte (CTL) activity (1, 2, 4-7) or for cooperative helper T-cell function (3,8,9). In addition, we have analyzed B lymphocytes from such chimeras for evidence of adaptive differentiation similar to that observed with T lymphocytes, and have demonstrated this to be true (3,11). In general, the weight of evidence from all such studies makes it clear that lymphocytes do, indeed, differentiate adaptively in accordance with the MHC phenotype of the environment in which they live.…”