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.

scholarly journals Autoantibodies in chronic graft versus host result from cognate T-B interactions.

1990 ◽  
Vol 171 (2) ◽  
pp. 503-517 ◽  
Author(s):  
S C Morris ◽  
R L Cheek ◽  
P L Cohen ◽  
R A Eisenberg
Keyword(s):  
T Cells ◽  
B Cells ◽  
Direct Interaction ◽  
Graft Versus Host Reaction ◽  
Spleen Cells ◽  
Host Reaction ◽  
Graft Versus Host ◽  
Alloreactive T Cells ◽  
Donor T Cells ◽  
And Control

A chronic graft-versus-host reaction (GVH) induced in nonautoimmune mice causes a syndrome that closely resembles SLE. In this model, donor T cells react against incompatible host Ia structures and generate excessive help, which activates a subpopulation of self-reactive B cells. We have studied whether these self-reactive B cells are activated by direct interaction with alloreactive T cells or by nonspecific bystander effects. Two types of chimeras were made: double-parental chimeras, differing at both Ia and Igh allotype [B6.C20 + bm12----(B6.C20 x bm12)F1]; and control chimeras [(B6.C20 x bm12)F1----(B6.C20 x bm12)F1]. A chronic GVH syndrome was induced in the chimeras by infusion of B6 or bm12 spleen cells. Coombs and antichromatin autoantibodies were measured using Igh allotype-specific immunoassays. The double-parental chimeras that received bm12 cells made autoantibodies principally of the Igha allotype, indicating that the bm12 T cells interacted only with the Iab-bearing host B cells. Conversely, double-parental chimeras that received B6 cells made mostly Ighb autoantibodies, indicating direct cognate interaction with the Iabm12-bearing host B cells. The control chimeras made autoantibodies of both allotypes. These results indicate that autoantibodies in chronic GVH result from direct T-B interactions and not from nonspecific T cell-derived factors.

scholarly journals Suppression of B-cell development as a result of selective expansion of donor T cells during the minor H antigen graft-versus-host reaction

Blood ◽  
1993 ◽  
Vol 82 (9) ◽  
pp. 2758-2766 ◽  
Author(s):  
BA Garvy ◽  
JM Elia ◽  
BL Hamilton ◽  
RL Riley
Keyword(s):  
T Cells ◽  
B Cells ◽  
B Cell ◽  
Cell Development ◽  
B Cell Development ◽  
Graft Versus Host Reaction ◽  
Host Reaction ◽  
Ifn Gamma ◽  
Graft Versus Host ◽  
B Lineage

Abstract A murine model of bone marrow (BM) transplantation in which donor (B10.D2) and recipient (BALB/c) mice were major histocompatibility complex (MHC) (H-2d) and Mls-1 identical, but incompatible at multiple non-MHC minor histocompatibility (H) antigens, and at Mls-2,3 was used to examine regeneration of B-cell development during the minor H antigen graft-versus-host reaction (GVHR). Mice that received T-cell- depleted allogeneic BM regained significant pre-B cells (sIg- 14.8+) in their BM. Mice undergoing GVHR after transplantation with allogeneic BM + T cells had less than 2% pre-B cells in their BM at day 7 and only 12% to 14% pre-B cells at days 21 and 28 compared with greater than 20% pre-B cells in the allogeneic controls. After partial recovery, the pre- B cells in the BM of GVH mice again decreased to less than 3% by day 42. This abnormal pattern of pre-B cell development in mice undergoing GVHR was associated with a reduced response to interleukin-7 (IL-7) in vitro. The delay in B-lineage cell reconstitution in mice with GVHR correlated with the expansion of donor V beta 3+ T cells in both the spleen and BM. BM T cells from mice with GVHR as well as isolated V beta 3+ T cells inhibited IL-7 colony-forming units from normal BM in co-culture assays. This inhibition could be reversed with anti- interferon gamma (IFN gamma) antibody. These data suggest that the delay in appearance and the reduction in proportion and number of pre-B cells observed early during the GVH reaction in this model is caused, in part, by the inhibitory actions of IFN gamma derived from donor V beta 3+ T cells on B-lineage cell development.

scholarly journals Suppression of B-cell development as a result of selective expansion of donor T cells during the minor H antigen graft-versus-host reaction

Blood ◽  
1993 ◽  
Vol 82 (9) ◽  
pp. 2758-2766 ◽  
Author(s):  
BA Garvy ◽  
JM Elia ◽  
BL Hamilton ◽  
RL Riley
Keyword(s):  
T Cells ◽  
B Cells ◽  
B Cell ◽  
Cell Development ◽  
B Cell Development ◽  
Graft Versus Host Reaction ◽  
Host Reaction ◽  
Ifn Gamma ◽  
Graft Versus Host ◽  
B Lineage

A murine model of bone marrow (BM) transplantation in which donor (B10.D2) and recipient (BALB/c) mice were major histocompatibility complex (MHC) (H-2d) and Mls-1 identical, but incompatible at multiple non-MHC minor histocompatibility (H) antigens, and at Mls-2,3 was used to examine regeneration of B-cell development during the minor H antigen graft-versus-host reaction (GVHR). Mice that received T-cell- depleted allogeneic BM regained significant pre-B cells (sIg- 14.8+) in their BM. Mice undergoing GVHR after transplantation with allogeneic BM + T cells had less than 2% pre-B cells in their BM at day 7 and only 12% to 14% pre-B cells at days 21 and 28 compared with greater than 20% pre-B cells in the allogeneic controls. After partial recovery, the pre- B cells in the BM of GVH mice again decreased to less than 3% by day 42. This abnormal pattern of pre-B cell development in mice undergoing GVHR was associated with a reduced response to interleukin-7 (IL-7) in vitro. The delay in B-lineage cell reconstitution in mice with GVHR correlated with the expansion of donor V beta 3+ T cells in both the spleen and BM. BM T cells from mice with GVHR as well as isolated V beta 3+ T cells inhibited IL-7 colony-forming units from normal BM in co-culture assays. This inhibition could be reversed with anti- interferon gamma (IFN gamma) antibody. These data suggest that the delay in appearance and the reduction in proportion and number of pre-B cells observed early during the GVH reaction in this model is caused, in part, by the inhibitory actions of IFN gamma derived from donor V beta 3+ T cells on B-lineage cell development.

Reduced Graft-versus-Host Reaction of T Cells in Kaposi’s Sarcoma: A Possible Prognostic Indicator

Dermatology ◽  
1984 ◽  
Vol 169 (2) ◽  
pp. 76-79 ◽  
Author(s):  
Michael David ◽  
Batya Shohat ◽  
Gregory Morozinski ◽  
Eleasar J. Feuerman
Keyword(s):  
T Cells ◽  
Kaposi's Sarcoma ◽  
Kaposi’S Sarcoma ◽  
Prognostic Indicator ◽  
Graft Versus Host Reaction ◽  
Host Reaction ◽  
Graft Versus Host

scholarly journals GRAFT-VERSUS-HOST REACTION ACROSS DIFFERENT REGIONS OF THE H-2 COMPLEX OF THE MOUSE

1973 ◽  
Vol 137 (5) ◽  
pp. 1213-1225 ◽  
Author(s):  
Jan Klein ◽  
Jong M. Park
Keyword(s):  
T Cells ◽  
Mixed Lymphocyte Reaction ◽  
Graft Versus Host Reaction ◽  
Spleen Cells ◽  
Host Reaction ◽  
Graft Versus Host ◽  
D Region ◽  
The Individual ◽  
Ir Genes

H-2 crossovers and their parental strains were arranged into 35 combinations in which the adult donor of spleen cells differed from the newborn recipient in the whole H-2 complex, or in three, two, or one region of the complex. A Simonsen splenomegaly assay was then used to test the contribution of the individual H-2 regions to the graft-versus-host reaction (GVHR). It was shown that the strongest GVHR was associated with the Ir region. Differences in the Ir region caused significant splenomegaly in spite of the fact that no antigens detectable by conventional serological methods have thus far been associated with this region. Differences in the K and D regions showed only a borderline effect on GVHR in spite of the fact that these regions code for most, if not all, of the antigens detectable by conventional serological and transplantation methods. The K region alone caused no stronger GVHR than the D legion alone; however, K + Ir region differences led to much stronger GVHR than D region differences. The Ss-Slp region also showed only a borderline effect on GVHR. Differences in two or more H-2 regions usually caused greater splenomegaly than differences in each of the regions separately. On the basis of these findings it is concluded that the strongest GVHR is caused by genes distinct from the known histocompatibility genes of the H-2 complex. It is speculated that the GVHR genes are identical with the mixed lymphocyte reaction (MLR) and Ir genes and that the product of these genes are receptors on the surface of the thymus-derived lymphocytes (T cells).

The role of B cells in the pathogenesis of graft-versus-host disease

Blood ◽  
2009 ◽  
Vol 114 (24) ◽  
pp. 4919-4927 ◽  
Author(s):  
Alexander Shimabukuro-Vornhagen ◽  
Michael J. Hallek ◽  
Rainer F. Storb ◽  
Michael S. von Bergwelt-Baildon
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
B Cells ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Chronic Gvhd ◽  
Graft Versus Host Reaction ◽  
Hematopoietic Stem ◽  
Graft Versus Host

Abstract Allogeneic hematopoietic stem cell transplantation is an established treatment modality for malignant and nonmalignant hematologic diseases. Acute and chronic graft-versus-host diseases (GVHDs) are a major cause of morbidity and mortality after allogeneic stem cell transplantation. T cells have been identified as key players in the graft-versus-host reaction and, therefore, most established drugs used against GVHD target T cells. Despite our knowledge on the pathogenesis of the GVH reaction, success of established therapies for prevention and treatment of GHVD is unsatisfactory. Recently, animal and human studies demonstrated that B cells are involved in the immunopathophysiology of acute and chronic GVHD. Early phase clinical trials of B-cell depletion with rituximab have shown beneficial effects on both acute and chronic GVHD. This review summarizes the current experimental and clinical evidence for the involvement of B cells in the pathogenesis of acute and chronic GVHD and discusses the clinical implications for the management of patients undergoing allogeneic stem cell transplantation.

Sign in / Sign up

Export Citation Format

Share Document