Coexpression of B7-1 and antigen blocks tolerance induction to antigen presented by resting B cells
UMass Chan Affiliations
Graduate School of Biomedical SciencesDepartment of Molecular Genetics and Microbiology
Document Type
Journal ArticlePublication Date
1996-09-01Keywords
Animals; *Antigen Presentation; Antigen-Presenting Cells; Antigens, CD80; B-Lymphocytes; Female; Humans; Immunization, Secondary; Immunoglobulin mu-Chains; Injections, Intravenous; Interphase; Lipopolysaccharides; *Lymphocyte Activation; Lymphocyte Transfusion; Male; Mice; Mice, Transgenic; *Self ToleranceLife Sciences
Medicine and Health Sciences
Metadata
Show full item recordAbstract
To investigate a role for B cells as tolerogenic APCs in peripheral lymphoid organs, we have developed a system in which B cells from mice transgenic for the membrane-bound form of human mu-chain are transferred into nontransgenic recipients. Mice injected with B cells expressing human mu-chain became profoundly tolerant to human mu-chain, as shown by greatly reduced Ab responses following challenge with human mu-chain in adjuvant. Adoptive transfer experiments showed that the recipient's Th cell response to human mu-chain was impaired. When the human mu transgenic spleen cells were activated with LPS before transfer, they no longer induced tolerance. Spleen cells from double-transgenic mice expressing both human mu-chain and the costimulatory molecule B7-1 (CD80) also failed to induce tolerance to human mu-chain. However, neither human mu transgenic LPS blasts nor double-transgenic B cells induced an Ab response or primed for a secondary Ab response to Ag in adjuvant. Therefore, we find that expression of B7-1 together with Ag can interfere with tolerance induction without inducing Ab formation or priming for a secondary Ab response.Source
J Immunol. 1996 Sep 1;157(5):1987-95.
Permanent Link to this Item
http://hdl.handle.net/20.500.14038/34058PubMed ID
8757319Related Resources
Related items
Showing items related by title, author, creator and subject.
-
A new isolation method for rat intraepithelial lymphocytesTodd, Derrick James; Singh, Amrik J.; Greiner, Dale L.; Mordes, John P.; Rossini, Aldo A.; Bortell, Rita (1999-06-05)Intraepithelial lymphocytes (IELs) play critical roles in gut immunity. In mice, gammadelta T cells are a large component of the IEL population. In the rat, gammadelta IELs are reportedly much less common, but technical issues suggest that previous analyses should be interpreted cautiously. The study of IELs in rats has been impeded by isolation procedures that are lengthy and complex, leading to small cell yields. For this reason, it is possible that rat IELs analyzed in previous studies have not been representative of the entire IEL compartment. We report a new method for the isolation of rat IELs that is based on the selective removal of intestinal epithelial cells under conditions that leave the basement membrane undisturbed. The method is rapid and requires neither enzymatic digestion, nor surgical removal of Peyer's patches, nor vigorous mechanical manipulation of the intestine. The yield of rat IELs using this method is 5- to 10-fold greater than that reported for other methods. Morphological and phenotypic analyses demonstrated that the purified cell population is comprised of IELs and is not contaminated with lamina propria or Peyer's patch lymphocytes. Phenotypic analysis revealed five major subsets of IELs based on differential cell surface expression of CD4, CD8, and alphabeta T cell receptor (TcR). Among the alphabetaTcR- cells was a population of gammadelta T cells present at levels not previously detected. The isolation of IEL sub-populations using this methodology should facilitate studies of the function of these cells in gut immunity.
-
Activation of MAP-2 kinase activity by the CD2 receptor in Jurkat T cells can be reversed by CD45 phosphataseNel, Andre E.; Ledbetter, Jeffrey A.; Williams, Katherine; Ho, P.; Akerley, Brian J.; Franklin, Kymberly; Katz, Rina (1991-06-01)We have recently characterized a serine kinase in T lymphocytes which phosphorylates microtubule-associated protein-2 (MAP-2) in vitro. This kinase is activated in a rapidly reversible fashion during ligation of CD3/Ti by a process which involves tyrosine phosphorylation of the enzyme itself. We show that the stimulatory anti-CD2 mAb combination, anti-(T11(2) + T11(3), stimulates MAP-2K activity in Jurkat cells with kinetics that are more prolonged than during anti-CD3 treatment. The principal difference is not in the rate of response induction, but in the decline of the response beyond the peak, to which end anti-CD2 stimulation resembles the sustained phytohaemagglutin (PHA) response. Parallel immunoblotting, utilizing anti-phosphotyrosine antibodies, also revealed differences in the rate at which tyrosine phosphorylation of pp43 (MAP-2K) disappears after induction. In spite of these differences, CD2 was absolutely dependent on the presence of CD3 for inducing a MAP-2K response in Jurkat cells. These results indicate that, even though CD2 and CD3 are using a common signalling pathway in Jurkat cells, additional differences such as the involvement of a tyrosine phosphatase may have to be considered in response generation. We also demonstrate that the common CD45 isoform, when cross-linked to CD2 by mAb, could inhibit the MAP-2K response during both induction as well as the disappearing phase of the response.
-
Evidence for involvement of glycoprotein-CD45 phosphatase in reversing glycoprotein-CD3-induced microtubule-associated protein-2 kinase activity in Jurkat T-cellsPollack, Shimon; Ledbetter, Jeffrey A.; Katz, Rina; Williams, Katherine; Akerley, Brian J.; Franklin, Kymberly; Schieven, Gary L.; Nel, Andre E. (1991-06-01)Ligation of CD3/TCR on T-cells induces transient activation of lymphoid MAP-2 kinase (MAP-2K), a 43 kDa serine kinase which itself is a substrate of an unidentified tyrosine kinase (pp43). The reversibility of the MAP-2K response agrees with removal of tyrosine phosphates from pp43. Since both activity as well as tyrosine phosphorylation of MAP-2K could be prolonged by Na3VO4, a phosphotyrosine phosphatase inhibitor, we studied the effect of the common CD45 isoform, which is a member of the CD45 phosphatase family, on MAP-2K activity in vivo and in vitro. We demonstrate the ability of purified CD45 phosphatase to remove tyrosine phosphates from partially purified lymphoid MAP-2K. Utilizing the approach of heterologous receptor aggregation, we also showed that CD45 could inhibit the induction of MAP-2K activity in intact Jurkat cells during CD3 or CD3 + CD4 stimulation. We therefore suggest that this phosphatase may control the activity of lymphoid MAP-2K in vivo.