Abstract
The present study has evaluated the identity of the B cell subpopulations participating in T dependent antibody responses that differ in their requirements for major histocompatibility complex-restricted T cell recognition. In vitro responses of keyhole limpet hemocyanin (KLH)-primed T cells and trinitrophenyl (TNP)-primed B cells were studied to both low and high concentrations of the antigen TNP-KLH. It was first demonstrated that for responses to low concentrations of TNP-KLH, (A × B)F(1) {arrow} parent(A) chimeric helper T cells were restricted in their ability to recognize parent(A) but not parent(B) H-2 determinants expressed by both B cells and antigen-presenting cells (APC). In contrast, at higher antigen concentrations, helper T cells were not restricted in their interaction with B cells. It was then determined whether these observed differences in T cell recognition resulted from the activation of distinct B cell subpopulations with different activation requirements. At low concentrations of TNP-KLH it was demonstrated that Lyb-5(-) B cells were activated, and that it was thus the activation of the Lyb-5(-) subpopulation that required T cell recognition of B cell H-2 under these conditions. In contrast, responses to high concentration of antigen required the participation of Lyb-5(+) B cells, and these Lyb-5(+) B cells were activated by a pathway that required H-2- restricted T cell interaction with APC, but not with B cells. The findings presented here have demonstrated that Lyb-5(-) and Lyb-5(+) B cells constitute B cell subpopulations that differ significantly in their activation requirements for T cell-dependent antibody responses to TNP-KLH. In so doing, these findings have established that the function of genetic restrictions in immune response regulation is critically dependent upon the activation pathways employed by functionally distinct subpopulations of B, as well as T, lymphocytes.
Full Text
The Full Text of this article is available as a PDF (954.1 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Ahmed A., Scher I., Sharrow S. O., Smith A. H., Paul W. E., Sachs D. H., Sell K. W. B-lymphocyte heterogeneity: development and characterization of an alloantiserum which distinguishes B-lymphocyte differentiation alloantigens. J Exp Med. 1977 Jan 1;145(1):101–110. doi: 10.1084/jem.145.1.101. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Boswell H. S., Ahmed A., Scher I., Singer A. Role of accessory cells in B cell activation. II. The interaction of B cells with accessory cells results in the exclusive activation of an Lyb5+ B cell subpopulation. J Immunol. 1980 Sep;125(3):1340–1348. [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]
- Erb P., Feldmann M. The role of macrophages in the generation of T-helper cells. II. The genetic control of the macrophage-T-cell interaction for helper cell induction with soluble antigens. J Exp Med. 1975 Aug 1;142(2):460–472. doi: 10.1084/jem.142.2.460. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Erb P., Meier B., Matsunaga T., Feldmann M. Nature of T-cell macrophage interaction in helper-cell induction in vitro. II. Two stages of T-helper-cell differentiation analyzed in irradiation and allophenic chimeras. J Exp Med. 1979 Mar 1;149(3):686–701. doi: 10.1084/jem.149.3.686. [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]
- Huber B., Gershon R. K., Cantor H. Identification of a B-cell surface structure involved in antigen-dependent triggering: absence of this structure on B cells from CBA/N mutant mice. J Exp Med. 1977 Jan 1;145(1):10–20. doi: 10.1084/jem.145.1.10. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Julius M. H., Simpson E., Herzenberg L. A. A rapid method for the isolation of functional thymus-derived murine lymphocytes. Eur J Immunol. 1973 Oct;3(10):645–649. doi: 10.1002/eji.1830031011. [DOI] [PubMed] [Google Scholar]
- Lewis G. K., Goodman J. W., Ranken R. Activation of B cell subsets by T-dependent and T-independent antigens. Adv Exp Med Biol. 1978;98:339–356. doi: 10.1007/978-1-4615-8858-0_18. [DOI] [PubMed] [Google Scholar]
- Mage M. G., McHugh L. L., Rothstein T. L. Mouse lymphocytes with and without surface immunoglobulin: preparative scale separation in polystyrene tissue culture dishes coated with specifically purified anti-immunoglobulin. J Immunol Methods. 1977;15(1):47–56. doi: 10.1016/0022-1759(77)90016-3. [DOI] [PubMed] [Google Scholar]
- McDougal J. S., Cort S. P. Generation of T helper cells in vitro. IV. F1 T helper cells primed with antigen-pulsed parental macrophages are genetically restricted in their antigen-specific helper activity. J Immunol. 1978 Feb;120(2):445–451. [PubMed] [Google Scholar]
- Melchers F., Andersson J., Lernhardt W., Schreier M. H. H-2-unrestricted polyclonal maturation without replication of small B cells induced by antigen-activated T cell help factors. Eur J Immunol. 1980 Sep;10(9):679–685. doi: 10.1002/eji.1830100905. [DOI] [PubMed] [Google Scholar]
- Pierce S. K., Klinman N. R. The allogeneic bisection of carrier-specific enhancement of monoclonal B-cell responses. J Exp Med. 1975 Nov 1;142(5):1165–1179. doi: 10.1084/jem.142.5.1165. [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]
- Shih W. W., Matzinger P. C., Swain S. L., Dutton R. W. Analysis of histocompatibility requirements for proliferative and helper T cell activity. T cell populations depleted of alloreactive cells by negative selection. J Exp Med. 1980 Nov 1;152(5):1311–1328. doi: 10.1084/jem.152.5.1311. [DOI] [PMC free article] [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]
- Singer A., Hathcock K. S., Hodes R. J. Cellular and genetic control of antibody responses. VIII. MHC restricted recognition of accessory cells, not B cells, by parent-specific subpopulations of normal F1 T helper cells. J Immunol. 1980 Mar;124(3):1079–1085. [PubMed] [Google Scholar]
- Sprent J. Restricted helper function of F1 hybrid T cells positively selected to heterologous erythrocytes in irradiated parental strain mice. I. Failure to collaborate with B cells of the opposite parental strain not associated with active suppression. J Exp Med. 1978 Apr 1;147(4):1142–1158. doi: 10.1084/jem.147.4.1142. [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]
- Subbarao B., Ahmed A., Paul W. E., Scher I., Lieberman R., Mosier D. E. Lyb-7, a new B cell alloantigen controlled by genes linked to the IgCH locus. J Immunol. 1979 Jun;122(6):2279–2285. [PubMed] [Google Scholar]
- Swierkosz J. E., Rock K., Marrack P., Kappler J. W. The role of H-2 linked genes in helper T-cell function. II. Isolation on antigen-pulsed macrophages of two separate populations of F1 helper T cells each specific for antigen and one set of parental H-2 products. J Exp Med. 1978 Feb 1;147(2):554–570. doi: 10.1084/jem.147.2.554. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yamashita U., Shevach E. M. The histocompatibility restrictions on macrophage T-helper cell interaction determine the histocompatibility restrictions on T-helper cell B-cell interaction. J Exp Med. 1978 Nov 1;148(5):1171–1185. doi: 10.1084/jem.148.5.1171. [DOI] [PMC free article] [PubMed] [Google Scholar]