Abstract
Several experimental approaches, designed specifically to circumvent the possible contribution of a complicating "allogeneic effect," have been successfully used to answer the question of physiologic cooperative interactions between histoincompatible T and B lymphocytes in antibody responses to hapten-protein conjugates. This was accomplished for in vivo cell transfer studies by using an F1 hybrid host as the recipient of irradiated, carrier-primed T lymphocytes from one parent and 2,4-dinitrophenyl (DNP)-primed B lymphocytes from the opposite strain. Under these conditions, very good T-B cell cooperative interactions were observed to occur between T and B lymphocyte populations derived from syngeneic donors, whereas no cooperative response was obtained when T cells were derived from one parental strain and B cells from the other. Corroborative experiments were performed in a totally in vitro system in which DNP-primed B cells developed good secondary anti-DNP antibody responses in vitro to soluble DNP-keyhole limpet hemocyanin (KLH) when cultured in the presence of irradiated KLH-primed T cells derived from syngenic donors but not from allogeneic donors. The failure of histoincompatible T and B lymphocytes to effect physiologic cooperative interactions has important implications for our understanding of how such interactions normally occur. The possibility that these results reflect the existence of a "block" of some sort to cell-cell interaction by virtue of the presence of a foreign major histocompatibility antigen on the surface of either cell has been definitively ruled out in the present studies. These observations demonstrate that the gene(s) that conditions the capability for physiologic T-B cell cooperation must be shared in common by the respective cell types, and suggest, furthermore, that this gene (or genes) belongs to the major histocompatibility system of the mouse. These findings, together with other relevant phenomena described previously, have led us to postulate that there exists on the B lymphocyte surface an "acceptor" molecule either for the putative active T cell product or for the T cell itself. The important genetic considerations and the possible sequence of events surrounding the actual T-B cell interaction implied by these postulates are discussed in detail.
Full Text
The Full Text of this article is available as a PDF (806.7 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Feldmann M. Cell interactions in the immune response in vitro. V. Specific collaboration via complexes of antigen and thymus-derived cell immunoglobulin. J Exp Med. 1972 Oct 1;136(4):737–760. doi: 10.1084/jem.136.4.737. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gorczynski R. M., Miller R. G., Phillips R. A. Initiation of antibody production to sheep erythrocytes in vitro: replacement of the requirement for T-cells with a cell-free factor isolated from cultures of lymphoid cells. J Immunol. 1972 Feb;108(2):547–551. [PubMed] [Google Scholar]
- Hamaoka T., Osborne D. P., Jr, Katz D. H. Cell interactions between histoincompatible T and B lymphocytes. I. Allogeneic effect by irradiated host T cells on adoptively transferred histoincompatible B lymphocytes. J Exp Med. 1973 Jun 1;137(6):1393–1404. doi: 10.1084/jem.137.6.1393. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Katz D. H., Benacerraf B. The regulatory influence of activated T cells on B cell responses to antigen. Adv Immunol. 1972;15:1–94. doi: 10.1016/s0065-2776(08)60683-5. [DOI] [PubMed] [Google Scholar]
- Katz D. H., Osborne D. P., Jr The allogeneic effect in inbred mice. II. Establishment of the cellular interactions required for enhancement of antibody production by the graft-versus-host reaction. J Exp Med. 1972 Sep 1;136(3):455–465. doi: 10.1084/jem.136.3.455. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Katz D. H. The allogeneic effect on immune responses: model for regulatory influences of T lymphocytes on the immune system. Transplant Rev. 1972;12:141–179. doi: 10.1111/j.1600-065x.1972.tb00055.x. [DOI] [PubMed] [Google Scholar]
- Katz D. H., Unanue E. R. Critical role of determinant presentation in the induction of specific responses in immunocompetent lymphocytes. J Exp Med. 1973 Apr 1;137(4):967–990. doi: 10.1084/jem.137.4.967. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kindred B., Shreffler D. C. H-2 dependence of co-operation between T and B cells in vivo. J Immunol. 1972 Nov;109(5):940–943. [PubMed] [Google Scholar]
- Mishell R. I., Dutton R. W. Immunization of normal mouse spleen cell suspensions in vitro. Science. 1966 Aug 26;153(3739):1004–1006. doi: 10.1126/science.153.3739.1004. [DOI] [PubMed] [Google Scholar]
- Plotz P. H., Talal N., Asofsky R. Assignment of direct and facilitated hemolytic plaques in mice to specific immunoglobulin classes. J Immunol. 1968 Apr;100(4):744–751. [PubMed] [Google Scholar]
- Rittenberg M. B., Pratt K. L. Antitrinitrophenyl (TNP) plaque assay. Primary response of Balb/c mice to soluble and particulate immunogen. Proc Soc Exp Biol Med. 1969 Nov;132(2):575–581. doi: 10.3181/00379727-132-34264. [DOI] [PubMed] [Google Scholar]
- Schimpl A., Wecker E. Replacement of T-cell function by a T-cell product. Nat New Biol. 1972 May 3;237(70):15–17. doi: 10.1038/newbio237015a0. [DOI] [PubMed] [Google Scholar]