Abstract
We have examined the carrier-specific helper activity of a number of antigen-specific, I region-restricted T cell hybridomas prepared in our laboratory. The hybridomas were assayed for helper activity in the presence or absence of exogenously added nonspecific factors found in the concanavalin A-activated supernatants of normal mouse spleen cells. Of six hybridomas tested, all six could stimulate the IgM anti-hapten response of hapten-primed B cells in the presence of the appropriate hapten-carrier conjugates. At low or moderate carrier doses, the response was dependent upon hapten-carrier linkage and the ability of the hybridoma cells to interact with carrier in association with H-2 products of the responding B cells themselves. Plaque-forming cell responses stimulated by some of the hybridomas were absolutely dependent upon the addition of nonspecific factors, suggesting that anti hapten-protein responses require both an antigen specific I region restricted signal from the T cell hybridomas and nonspecific helper factors, made either by the T cell hybridomas or added exogenously. Under two sets of circumstances, B cells were stimulated in the absence of a simultaneous signal delivered through their immunoglobulin receptor. This occurred either when hapten-primed B cells were stimulated with an ovalbumin/I-Ak-specific hybridoma in the presence of very high concentrations of ovalbumin, or when H-2b B cells were incubated with a hybridoma specific for I-Ab alone. This was interpreted to mean that B cells can be stimulated by reaction of T cells with surface I molecules.
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- Augustin A. A., Coutinho A. Specific T helper cells that activate B cells polyclonally. In vitro enrichment and cooperative function. J Exp Med. 1980 Mar 1;151(3):587–601. doi: 10.1084/jem.151.3.587. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Benacerraf B. A hypothesis to relate the specificity of T lymphocytes and the activity of I region-specific Ir genes in macrophages and B lymphocytes. J Immunol. 1978 Jun;120(6):1809–1812. [PubMed] [Google Scholar]
- Boswell H. S., Nerenberg M. I., Scher I., Singer A. Role of accessory cells in B cell activation. III. Cellular analysis of primary immune response deficits in CBA/N mice: presence of an accessory cell-B cell interaction defect. J Exp Med. 1980 Nov 1;152(5):1194–1309. doi: 10.1084/jem.152.5.1194. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cammisuli S., Henry C., Wofsy L. Role of membrane receptors in the induction of an in vitro secondary anti-hapten response. I. differentiation of B memory cells to plasma cells is independent of antigen-immunoglobulin receptor interaction. Eur J Immunol. 1978 Sep;8(9):656–662. doi: 10.1002/eji.1830080910. [DOI] [PubMed] [Google Scholar]
- Corradin G., Etlinger H. M., Chiller J. M. Lymphocyte specificity to protein antigens. I. Characterization of the antigen-induced in vitro T cell-dependent proliferative response with lymph node cells from primed mice. J Immunol. 1977 Sep;119(3):1048–1053. [PubMed] [Google Scholar]
- 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]
- Glimcher L. H., Kim K. J., Green I., Paul W. E. Ia antigen-bearing B cell tumor lines can present protein antigen and alloantigen in a major histocompatibility complex-restricted fashion to antigen-reactive T cells. J Exp Med. 1982 Feb 1;155(2):445–459. doi: 10.1084/jem.155.2.445. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Greaves M. F., Brown G. Purification of human T and B lymphocytes. J Immunol. 1974 Jan;112(1):420–423. [PubMed] [Google Scholar]
- Harwell L., Kappler J. W., Marrack P. Antigen-specific and nonspecific mediators of T cell/B cell cooperation. III. Characterization of the nonspecific mediator(s) from different sources. J Immunol. 1976 May;116(5):1379–1384. [PubMed] [Google Scholar]
- Harwell L., Skidmore B., Marrack P., Kappler J. Concanavalin A-inducible, interleukin-2-producing T cell hybridoma. J Exp Med. 1980 Oct 1;152(4):893–904. doi: 10.1084/jem.152.4.893. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hodes R. J., Singer A. Cellular and genetic control of antibody responses in vitro. I. Cellular requirements for the generation of genetically controlled primary IgM responses to soluble antigens. Eur J Immunol. 1977 Dec;7(12):892–897. doi: 10.1002/eji.1830071214. [DOI] [PubMed] [Google Scholar]
- Hoffmann M. K., Watson J. Helper T cell-replacing factors secreted by thymus-derived cells and macrophages: cellular requirements for B cell activation and synergistic properties. J Immunol. 1979 Apr;122(4):1371–1375. [PubMed] [Google Scholar]
- Hunter P. M., Kappler J. W., Kettman J. R. The frequency and activity of single helper T cells. J Immunol. 1974 Sep;113(3):830–834. [PubMed] [Google Scholar]
- Isakson P. C., Puré E., Uhr J. W., Vitetta E. S. Induction of proliferation and differentiation of neoplastic B cells by anti-immunoglobulin and T-cell factors. Proc Natl Acad Sci U S A. 1981 Apr;78(4):2507–2511. doi: 10.1073/pnas.78.4.2507. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jones B., Janeway C. A., Jr Cooperative interaction of B lymphocytes with antigen-specific helper T lymphocytes is MHC restricted. Nature. 1981 Aug 6;292(5823):547–549. doi: 10.1038/292547a0. [DOI] [PubMed] [Google Scholar]
- Kappler J. W., Marrack P. C. Helper T cells recognise antigen and macrophage surface components simultaneously. Nature. 1976 Aug 26;262(5571):797–799. doi: 10.1038/262797a0. [DOI] [PubMed] [Google Scholar]
- Kappler J. W., Skidmore B., White J., Marrack P. Antigen-inducible, H-2-restricted, interleukin-2-producing T cell hybridomas. Lack of independent antigen and H-2 recognition. J Exp Med. 1981 May 1;153(5):1198–1214. doi: 10.1084/jem.153.5.1198. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Keller D. M., Swierkosz J. E., Marrack P., Kappler J. W. Two types of functionally distinct, synergizing helper T cells. J Immunol. 1980 Mar;124(3):1350–1359. [PubMed] [Google Scholar]
- Kettman J., Dutton R. W. An in vitro primary immune response to 2,4,6-trinitrophenyl substituted erythrocytes: response against carrier and hapten. J Immunol. 1970 Jun;104(6):1558–1561. [PubMed] [Google Scholar]
- Leibson H. J., Marrack P., Kappler J. W. B cell helper factors. I. Requirement for both interleukin 2 and another 40,000 mol wt factor. J Exp Med. 1981 Nov 1;154(5):1681–1693. doi: 10.1084/jem.154.5.1681. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Marrack P. C., Kappler J. W. Antigen-specific and nonspecific mediators of T cell/B cell cooperation. I. Evidence for their production by different T cells. J Immunol. 1975 Mar;114(3):1116–1125. [PubMed] [Google Scholar]
- Marrack P., Kappler J. W. The role of H-2-linked genes in helper T cell function. VII. Expression of I region and immune response genes by B cells in bystander help assays. J Exp Med. 1980 Nov 1;152(5):1274–1288. doi: 10.1084/jem.152.5.1274. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Marrack P., Kappler J. W. The role of H-2-linked genes in helper T-cell function. III. Expression of immune response genes for trinitrophenyl conjugates of poly-L(Tyr, Glu)-poly-D,L-Ala--poly-L-Lys in B cells and macrophages. J Exp Med. 1978 Jun 1;147(6):1596–1610. doi: 10.1084/jem.147.6.1596. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mishell R. I., Dutton R. W. Immunization of dissociated spleen cell cultures from normal mice. J Exp Med. 1967 Sep 1;126(3):423–442. doi: 10.1084/jem.126.3.423. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mitchison N. A. The carrier effect in the secondary response to hapten-protein conjugates. II. Cellular cooperation. Eur J Immunol. 1971 Jan;1(1):18–27. doi: 10.1002/eji.1830010104. [DOI] [PubMed] [Google Scholar]
- North J. R., Kemshead J. T., Askonas B. A. Non-specific factor replaces T cells in an IgG response to soluble antigens. Immunology. 1977 Sep;33(3):321–329. [PMC free article] [PubMed] [Google Scholar]
- Parker D. C., Wadsworth D. C., Schneider G. B. Activation of murine B lymphocytes by anti-immunoglobulin is an inductive signal leading to immunoglobulin secretion. J Exp Med. 1980 Jul 1;152(1):138–150. doi: 10.1084/jem.152.1.138. [DOI] [PMC free article] [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]
- Singer A., Hathcock K. S., Hodes R. J. Cellular and genetic control of antibody responses. V. Helper T-cell recognition of H-2 determinants on accessory cells but not B cells. J Exp Med. 1979 May 1;149(5):1208–1226. doi: 10.1084/jem.149.5.1208. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sprent J. Restricted helper function of F1 hybrid T cells positively selected to heterologous erythrocytes in irradiated parental strain mice. II. Evidence for restrictions affecting helper cell induction and T-B collaboration, both mapping to the K-end of the H-2 complex. J Exp Med. 1978 Apr 1;147(4):1159–1174. doi: 10.1084/jem.147.4.1159. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Swain S. L., Dennert G., Warner J. F., Dutton R. W. Culture supernatants of a stimulated T-cell line have helper activity that acts synergistically with interleukin 2 in the response of B cells to antigen. Proc Natl Acad Sci U S A. 1981 Apr;78(4):2517–2521. doi: 10.1073/pnas.78.4.2517. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Swierkosz J. E., Marrack P., Kappler J. W. Functional analysis of T cells expressing Ia antigens. I. Demonstration of helper T-cell heterogeneity. J Exp Med. 1979 Dec 1;150(6):1293–1309. doi: 10.1084/jem.150.6.1293. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Swierkosz J. E., Marrack P., Kappler J. W. The role of H-2-linked genes in helper T cell function. V. I-region control of helper T cell interaction with antigen-presenting macrophages. J Immunol. 1979 Aug;123(2):654–659. [PubMed] [Google Scholar]
- Tada T., Takemori T., Okumura K., Nonaka M., Tokuhisa T. Two distinct types of helper T cells involved in the secondary antibody response: independent and synergistic effects of Ia- and Ia+ helper T cells. J Exp Med. 1978 Feb 1;147(2):446–458. doi: 10.1084/jem.147.2.446. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Waldmann H., Munro A. T cell-dependent mediator in the immune response. II. Physical and biological properties. Immunology. 1974 Jul;27(1):53–64. [PMC free article] [PubMed] [Google Scholar]
- Walker E., Warner N. L., Chesnut R., Kappler J., Marrack P. Antigen-specific. I region-restricted interactions in vitro between tumor cell lines and T cell hybridomas. J Immunol. 1982 May;128(5):2164–2169. [PubMed] [Google Scholar]
- Watson J., Gillis S., Marbrook J., Mochizuki D., Smith K. A. Biochemical and biological characterization of lymphocyte regulatory molecules. I. Purification of a class of murine lymphokines. J Exp Med. 1979 Oct 1;150(4):849–861. doi: 10.1084/jem.150.4.849. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wood D. D., Cameron P. M. Stimulation of the release of a B cell-activating factor from human monocytes. Cell Immunol. 1976 Jan;21(1):133–145. doi: 10.1016/0008-8749(76)90334-8. [DOI] [PubMed] [Google Scholar]
