Induction of self-tolerance in T cells but not B cells of transgenic mice expressing little self antigen

Science ◽  
1991 ◽  
Vol 251 (4998) ◽  
pp. 1223-1225 ◽  
Author(s):  
S Adelstein ◽  
H Pritchard-Briscoe ◽  
T. Anderson ◽  
J Crosbie ◽  
G Gammon ◽  
...  
Keyword(s):  
T Cells ◽  
B Cells ◽  
Transgenic Mice ◽  
Self Tolerance ◽  
Self Antigen

scholarly journals B cells solicit their own help from T cells.

1996 ◽  
Vol 183 (3) ◽  
pp. 891-899 ◽  
Author(s):  
B Stockinger ◽  
T Zal ◽  
A Zal ◽  
D Gray
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Transgenic Mice ◽  
Cell Receptor ◽  
Type Contact ◽  
Antigen Presenting ◽  
Self Antigen

We have made use of T cell receptor (TCR)-transgenic mice with CD4+ T cells expressing a receptor specific for the self-antigen C5 (fifth component of complement) to study the role of different antigen-presenting cells in the determination of CD4+ T cell effector type. Contact of T cells from C5 TCR-transgenic mice with C5 protein or C5 peptide in vivo or in vitro induces biased T helper cell (Th) 1 type responses resulting in exclusive production of high levels of interferon gamma and interleukin (IL) 2. Transgenic mice, in contrast to nontransgenic littermates, do not generate an antibody response to C5. We show in this paper that B cell presentation in vitro induces a switch to the Th2 subset indicated by production of IL-4, and targetting C5 to B cells in vivo results in the generation of C5-specific antibodies.

scholarly journals Induction of autoreactive B cells allows priming of autoreactive T cells.

1991 ◽  
Vol 173 (6) ◽  
pp. 1433-1439 ◽  
Author(s):  
R H Lin ◽  
M J Mamula ◽  
J A Hardin ◽  
C A Janeway
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Cytochrome C ◽  
Autoantibody Production ◽  
Autoreactive T Cells ◽  
Human Cytochrome ◽  
Self Tolerance ◽  
Human Cytochrome C

A novel mechanism for breaking T cell self tolerance is described. B cells induced to make autoantibody by immunization of mice with the non-self protein human cytochrome c can present the self protein mouse cytochrome c to autoreactive T cells in immunogenic form. This mechanism of breaking T cell self tolerance could account for the role of foreign antigens in breaking not only B cell but also T cell self tolerance, leading to sustained autoantibody production in the absence of the foreign antigen.

Self-Tolerance in B-Cells from Different Lines of Lysozyme Double-Transgenic Mice

1989 ◽  
pp. 377-384 ◽  
Author(s):  
A. Basten ◽  
R. A. Brink ◽  
D. Y. Mason ◽  
J. Crosbie ◽  
C. C. Goodnow
Keyword(s):  
B Cells ◽  
Transgenic Mice ◽  
Self Tolerance ◽  
Double Transgenic Mice

scholarly journals Immunoglobulin M and D antigen receptors are both capable of mediating B lymphocyte activation, deletion, or anergy after interaction with specific antigen.

1992 ◽  
Vol 176 (4) ◽  
pp. 991-1005 ◽  
Author(s):  
R Brink ◽  
C C Goodnow ◽  
J Crosbie ◽  
E Adams ◽  
J Eris ◽  
...  
Keyword(s):  
T Cell ◽  
B Cells ◽  
Transgenic Mice ◽  
B Lymphocyte ◽  
Specific Antigen ◽  
Antigen Receptors ◽  
Antigen B ◽  
Self Antigen ◽  
Clonal Anergy

A series of immunoglobulin (Ig)-transgenic mice were generated to study the functional capabilities of the IgM and IgD classes of B lymphocyte antigen receptor in regulating both cellular development and responses to specific antigen. B cells from Ig-transgenic mice expressing either hen-egg lysozyme (HEL)-specific IgM or IgD alone were compared with B cells from mice that coexpressed IgM and IgD of the same anti-HEL specificity. In all three types of Ig-transgenic mice, conventional B cells specific for HEL exhibited exclusion of endogenous Ig expression and matured to populate the usual microenvironments in peripheral lymphoid tissues. These peripheral B cells could be stimulated by HEL through either IgM or IgD antigen receptors to generate T cell dependent antibody production in vivo or to enhance T cell independent proliferative responses to lipopolysaccharide in vitro. Conversely, when HEL was encountered in vivo as a self-antigen, B cells expressing HEL-specific IgM or IgD alone were both rendered tolerant. In each case this occurred by clonal anergy in response to soluble autologous HEL, and clonal deletion when HEL was recognized as a membrane-bound self-antigen. Taken together, these findings indicate that IgM and IgD antigen receptors expressed alone on conventional B cells can support normal differentiation, antigen-dependent activation, and induction of self-tolerance, the only overt difference lying in a greater degree of receptor downregulation for IgM relative to IgD after induction of clonal anergy by soluble HEL.

scholarly journals Self-antigen presentation by mouse B cells results in regulatory T-cell induction rather than anergy or clonal deletion

Blood ◽  
2011 ◽  
Vol 118 (4) ◽  
pp. 984-991 ◽  
Author(s):  
Sara Morlacchi ◽  
Cristiana Soldani ◽  
Antonella Viola ◽  
Adelaida Sarukhan
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Antigen Expression ◽  
T Cell Tolerance ◽  
Cell Tolerance ◽  
Clonal Deletion ◽  
Thymic Epithelium ◽  
Self Antigen ◽  
Self Antigens

Abstract Multiple mechanisms operate to ensure T-cell tolerance toward self-antigens. Three main processes have been described: clonal deletion, anergy, and deviation to CD4+ regulatory T cells (Tregs) that suppress autoreactive T cells that have escaped the first 2 mechanisms. Although it is accepted that dendritic cells (DCs) and B cells contribute in maintaining T-cell tolerance to self-antigens, their relative contribution and the processes involved under physiologic conditions remain only partially characterized. In this study, we used different transgenic mouse models to obtain chimeras where a neo self-antigen is expressed by thymic epithelium and/or by DCs or B cells. We found that expression of cognate ligand in the thymus enhances antigen-specific FoxP3+ cells independently of whether the self-antigen is expressed on thymic epithelium or only on DCs, but not on B cells. On the contrary, self-antigen expression by B cells was very efficient in inducing FoxP3+ cells in the periphery, whereas self-antigen expression by DC led mainly to deletion and anergy of antigen-specific FoxP3− cells. The results presented in this study underline the role of B cells in Treg induction and may have important implications in clinical protocols aimed at the peripheral expansion of Tregs in patients.

scholarly journals Spontaneous relapsing-remitting EAE in the SJL/J mouse: MOG-reactive transgenic T cells recruit endogenous MOG-specific B cells

2009 ◽  
Vol 206 (6) ◽  
pp. 1303-1316 ◽  
Author(s):  
Bernadette Pöllinger ◽  
Gurumoorthy Krishnamoorthy ◽  
Kerstin Berer ◽  
Hans Lassmann ◽  
Michael R. Bösl ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Transgenic Mice ◽  
B Cell ◽  
Cell Receptor ◽  
Conformational Epitope ◽  
Autoreactive B Cells ◽  
Spinal Cord Development ◽  
Relapsing Remitting

We describe new T cell receptor (TCR) transgenic mice (relapsing-remitting [RR] mice) carrying a TCR specific for myelin oligodendrocyte glycoprotein (MOG) peptide 92–106 in the context of I-As. Backcrossed to the SJL/J background, most RR mice spontaneously develop RR experimental autoimmune encephalomyelitis (EAE) with episodes often altering between different central nervous system tissues like the cerebellum, optic nerve, and spinal cord. Development of spontaneous EAE depends on the presence of an intact B cell compartment and on the expression of MOG autoantigen. There is no spontaneous EAE development in B cell–depleted mice or in transgenic mice lacking MOG. Transgenic T cells seem to expand MOG autoreactive B cells from the endogenous repertoire. The expanded autoreactive B cells produce autoantibodies binding to a conformational epitope on the native MOG protein while ignoring the T cell target peptide. The secreted autoantibodies are pathogenic, enhancing demyelinating EAE episodes. RR mice constitute the first spontaneous animal model for the most common form of multiple sclerosis (MS), RR MS.

scholarly journals Light chain editing generates polyreactive antibodies in chronic graft-versus-host reaction

2006 ◽  
Vol 203 (7) ◽  
pp. 1761-1772 ◽  
Author(s):  
Esther J. Witsch ◽  
Hong Cao ◽  
Hidehiro Fukuyama ◽  
Martin Weigert
Keyword(s):  
T Cells ◽  
B Cells ◽  
Transgenic Mice ◽  
Marginal Zone ◽  
Basic Protein ◽  
Autoimmune Response ◽  
Graft Versus Host Reaction ◽  
Host Reaction ◽  
Graft Versus Host ◽  
Polyreactive Antibodies

The chronic graft-versus-host (cGvH) reaction is a model of induced lupus caused by alloreactive CD4+ T cells from a Bm-12 mouse in a C57BL/6 recipient. We used this cGvH reaction in C57BL/6 anti-DNA H chain transgenic mice, 56R/B6, to understand the structure, specificity, and origin of the induced autoantibodies (auto-Abs). We found anti-DNA Abs that reacted to several different antigens, such as phosphatidylserine, myelin basic protein, thyroglobulin, histone, insulin, cytochrome C, and β-galactosidase. This polyreactivity was found for Abs from B cells that expressed the 56R H chain transgene with “editor” L chains that did not completely veto autoreactivity. We suggest that such incomplete editing results in polyreactivity and that incompletely edited polyreactive B cells influence the subsequent expression of pathogenic auto-Abs in disease. We also found B cells that coexpress κ and λ L chain. These B cells contributed to the autoimmune response and are possibly in the marginal zone of the spleen.

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