Cell Interactions Between Histoincompatible T and B Lymphocytes. The H-2 Gene Complex Determines Successful Physiologic Lymphocyte Interactions

Abstract

We used congenic-resistant mouse strains to answer questions concerning the respective roles of genes coding for major histocompatibility and background genotypes in T (thymus-derived)-B (bone marrow-derived) lymphocyte cooperative responses to hapten-protein conjugates. These studies demonstrate conclusively that the gene or genes present in the H-2 complex control the capacity of antigen-specific T and B cells to effectively interact. These findings led us to postulate that there exists on the B-lymphocyte surface an "acceptor" molecule for the active T-cell product or for the T cell itself.

EVIDENCE FOR IDENTITY OR CLOSE ASSOCIATION OF THE Fc RECEPTOR OF B LYMPHOCYTES AND ALLOANTIGENS DETERMINED BY THE Ir REGION OF THE H-2 COMPLEX

“…Such factors are antigen specific, but there is conflicting evidence as to their biochemical nature (27,29). Finally, evidence has been obtained that in certain cases of Ir gene control, the defect in low responders appears to be expressed at the level of the B cell (29)(30)(31)(32). It has been proposed that such unresponsiveness at the B-cell level is to the haptenic determinant rather than the carrier portion of the immunogen (33).…”

Activation of T and B Lymphocytes in Vitro

“…In summary, as an extension of our previously stated hypothesis on this point (1,35,41,49), we envisage the following sequence involved in effective T-B-cell interactions: The antigen-activated T lymphocytes, in close proximity to the appropriate B cell, either engages direct contact at the specific acceptor site(s) on the B-cell surface and/or releases the active products (AEF) that have specific complementarity for, and bind to, the specific acceptor sites on the B lymphocyte. It is likely that the antigen-binding event on the specific B-cell surface Ig receptors has already taken place before the relevant interaction with the T cell occurs.…”

“…Recent observations demonstrating that most effective cooperative T-B-cell interactions occur when the respective cell populations possess identical genes located within the/t-2 gene complex led us to postulate the existence of a membrane "acceptor" site on the B-cell surface that interacts with either a complementary molecule existing either as a T-cell surface site or as a product released from the T cell (48)(49)(50). It occurred to us, therefore, that the active enhancing moiety in AEF might indeed represent one such molecule and, if so, should manifest some relationship to histocompatibility specificities.…”

Cellular Immune Recognition and the Biological Role of Major Transplantation Antigens

“…Our results were not the only ones that hinted at the biological role of major transplantation antigens, and they fitted several observations made during 1972/73. In addition to the suggestions from cytotoxic T-cell studies with leukaemia, ectromelia and LCM viruses [9, 40, 41, 41a] [43,44]. In parallel experiments with inbred strains of guinea pigs, A. S. Rosenthal and E. M. Shevach analysed antigen-specific proliferative T-cell responses and found them only when primed T-cells and antigen-presenting cells were from guinea pigs with the same MHC type [45].…”