Abstract
C3H/HeJ mice do not respond to the polyclonal B-cell activator lipopolysaccharide (LPS) from Escherichia coli; this was first described by Sultzer who observed that mice of this strain did not respond to an intraperitoneal (i.p.) injection of LPS as measured by the accumulation of leukocytes in the peritoneal cavity. Neither were C3H/HeJ mice as susceptible to LPS toxcitiy (1). It was later reported that LPS-induced mitogenesis (2,3), adjuvanticity (4), and the appearance of Ia antigens on B lymphocytes as induced by LPS, (5) was also absent in C3H/HeJ mice. However, lymphocytes from these mice respond normally to the polyclonal B-cell activators purified protein derivative of tuberculin (2,6) and dextran sulfate and have also been reported to respond normally to concanavalin A (Con A) (2). Furthermore, the immune responses to sheep erythrocytes (7) and soluble thymus-dependent antigens (4) are normal in C3H/HeJ mice. Unresponsiveness to LPS in C3H/HeJ mice has been found to Be due to a defect in a single gene or a set of linked genes (3,8) which has been mapped between the major urinary protein locus and the locus coding for polysyndactyly on chromosome 4. (1) We have reported that injection of LPS into mice of an LPS-responsive strain causes a shift in the Con A dose-response curve of cultured spleen cells, suppressing the low does response (9). Therefore, we tested the Con A proliferative response in cultures of normal or LPS-activated spleen cells from LPS-responder (C3H/Tif) and LPS-nonresponder (C3H/HeJ) mice. We report here that C3H/HeJ spleen cells respond poorly to low concentrations of Con A (0.05-0.1 μg/ml). Injection of LPS 2 days before culture inhibits the response to low doses of Con A in cultures of C3H/Tif spleen cells but has no inhibitory effect on the dose response profile of C3H/HeJ spleen cells. Furthermore, the low dose Con A response of spleen cells is dependent upon the presence of an Ia-positive cell. (2) The role of Ia-positive cells in the Con A response of C3H/Tif and C3H/HeJ spleen cells is described.
Full Text
The Full Text of this article is available as a PDF (443.8 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Coutinho A., Gronowicz E., Sultzer B. M. Genetic control of B-cell responses. I. Selective unresponsiveness to lipopolysaccharide. Scand J Immunol. 1975;4(2):139–143. doi: 10.1111/j.1365-3083.1975.tb02610.x. [DOI] [PubMed] [Google Scholar]
- Coutinho A., Moller G., Gronowicz E. Genetical control of B-cell responses. IV. Inheritance of the unresponsiveness to lipopolysaccharides. J Exp Med. 1975 Jul 1;142(1):253–258. doi: 10.1084/jem.142.1.253. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dutton R. W. Inhibitory and stimulatory effects of concanavalin A on the response of mouse spleen cell suspensions to antigen. I. Characterization of the inhibitory cell activity. J Exp Med. 1972 Dec 1;136(6):1445–1460. doi: 10.1084/jem.136.6.1445. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Forbes J. T., Nakao Y., Smith R. T. T mitogens trigger LPS responsiveness in mouse thymus cells. J Immunol. 1975 Mar;114(3):1004–1007. [PubMed] [Google Scholar]
- Frelinger J. A., Niederhuber J. E., Shreffler D. C. Effects of anti-Ia sera on mitogenic responses. III. Mapping the genes controlling the expression of Ia determinants on concanavalin A-reactive cells to the I-J subregion of the H-2 gene complex. J Exp Med. 1976 Oct 1;144(4):1141–1146. doi: 10.1084/jem.144.4.1141. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Greaves M. F., Möller E. Studies on antigen-binding cells. I. The origin of reactive cells. Cell Immunol. 1970 Oct;1(4):372–385. doi: 10.1016/0008-8749(70)90015-8. [DOI] [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]
- Ozato K., Adler W. H., Ebert J. D. Synergism of bacterial lipopolysaccharides and concanavalin A in the activation of thymic lymphocytes. Cell Immunol. 1975 Jun;17(2):532–541. doi: 10.1016/s0008-8749(75)80057-8. [DOI] [PubMed] [Google Scholar]
- Skidmore B. J., Chiller J. M., Morrison D. C., Weigle W. O. Immunologic properties of bacterial lipopolysaccharide (LPS): correlation between the mitogenic, adjuvant, and immunogenic activities. J Immunol. 1975 Feb;114(2 Pt 2):770–775. [PubMed] [Google Scholar]
- Sultzer B. M. Genetic control of leucocyte responses to endotoxin. Nature. 1968 Sep 21;219(5160):1253–1254. doi: 10.1038/2191253a0. [DOI] [PubMed] [Google Scholar]
- Sultzer B. M., Nilsson B. S. PPD tuberculin--a B-cell mitogen. Nat New Biol. 1972 Dec 13;240(102):198–200. doi: 10.1038/newbio240198a0. [DOI] [PubMed] [Google Scholar]
- Watson J., Riblet R. Genetic control of responses to bacterial lipopolysaccharides in mice. I. Evidence for a single gene that influences mitogenic and immunogenic respones to lipopolysaccharides. J Exp Med. 1974 Nov 1;140(5):1147–1161. doi: 10.1084/jem.140.5.1147. [DOI] [PMC free article] [PubMed] [Google Scholar]
