Conventional dendritic cells are the critical donor APC presenting alloantigen after experimental bone marrow transplantation

Blood ◽  
2009 ◽  
Vol 113 (22) ◽  
pp. 5644-5649 ◽  
Author(s):  
Kate A. Markey ◽  
Tatjana Banovic ◽  
Rachel D. Kuns ◽  
Stuart D. Olver ◽  
Alistair L. J. Don ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Dendritic Cells ◽  
Bone Marrow Transplantation ◽  
B Cells ◽  
Marrow Transplantation ◽  
Significant Contribution ◽  
Therapeutic Strategies ◽  
Relative Contribution ◽  
Histocompatibility Complex ◽  
Antigen Presenting

We have quantified the relative contribution of donor antigen-presenting cell populations to alloantigen presentation after bone marrow transplantation (BMT) by using transgenic T cells that can respond to host-derived alloantigen presented within the donor major histocompatibility complex. We also used additional transgenic/knockout donor mice and/or monoclonal antibodies that allowed conditional depletion of conventional dendritic cells (cDCs), plasmacytoid DC (pDCs), macrophages, or B cells. Using these systems, we demonstrate that donor cDCs are the critical population presenting alloantigen after BMT, whereas pDCs and macrophages do not make a significant contribution in isolation. In addition, alloantigen presentation was significantly enhanced in the absence of donor B cells, confirming a regulatory role for these cells early after transplantation. These data have major implications for the design of therapeutic strategies post-BMT, and suggest that cDC depletion and the promotion of B-cell reconstitution may be beneficial tools for the control of alloreactivity.

scholarly journals Follicular dendritic cells help resting B cells to become effective antigen-presenting cells: induction of B7/BB1 and upregulation of major histocompatibility complex class II molecules.

1993 ◽  
Vol 178 (6) ◽  
pp. 2055-2066 ◽  
Author(s):  
M H Kosco-Vilbois ◽  
D Gray ◽  
D Scheidegger ◽  
M Julius
Keyword(s):  
Dendritic Cells ◽  
Major Histocompatibility Complex ◽  
B Cells ◽  
Major Histocompatibility Complex Class ◽  
B Cell ◽  
Antigen Presenting Cells ◽  
Follicular Dendritic Cells ◽  
Complex Class ◽  
Histocompatibility Complex ◽  
Antigen Presenting

This study was designed to investigate whether follicular dendritic cells (FDC) can activate B cells to a state in which they can function as effective antigen-presenting cells (APC). High buoyant density (i.e., resting) B cells specific for 2,4-dinitro-fluorobenzene (DNP) were incubated with DNP-ovalbumin (OVA) bearing FDC, after which their capacity to process and present to an OVA-specific T cell clone was assessed. The efficacies of alternative sources of antigen and activation signals in the induction of B cell APC function were compared with those provided by FDC. Only FDC and Sepharose beads coated with anti-immunoglobulin (Ig)kappa monoclonal antibody provided the necessary stimulus. FDC carrying inappropriate antigens also induced B cell APC function in the presence of exogenous DNP-OVA. However, in circumstances where soluble DNP-OVA was limiting, FDC bearing complexes containing DNP, which could crosslink B cell Ig receptors, induced the most potent APC function. Analysis by flow cytometry revealed that within 24 h of coculture with FDC, a significant percentage of B cells increased in size and expressed higher levels of major histocompatibility complex class II. By 48 h, an upregulation of the costimulatory molecule, B7/BB1, occurred, but only when exposed to the FDC bearing DNP. Taken together, the results demonstrate that FDC have the capacity to activate resting B cells to a state in which they can function as APC for T cells. The stimuli that FDC provide may include: (a) an antigen-dependent signal that influences the upregulation of B7/BB1; and (b) possibly a signal independent of crosslinking mIg that results in Ig internalization. The relevance of these findings to the formation of germinal centers and maintenance of the humoral response is discussed.

scholarly journals B-cell dysfunction following human bone marrow transplantation: functional-phenotypic dissociation in the early posttransplant period

Blood ◽  
1989 ◽  
Vol 74 (2) ◽  
pp. 777-785 ◽  
Author(s):  
JM Kagan ◽  
RE Champlin ◽  
A Saxon
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
B Cells ◽  
Cell Surface ◽  
B Cell ◽  
Marrow Transplantation ◽  
Cell Activation ◽  
High Rate ◽  
Normal Surface ◽  
Surface Phenotype

Abstract We investigated the defect in humoral immunity that occurs following bone marrow transplantation (BMT). B cells from BMT recipients were tested for their ability to undergo the sequential steps of activation (RNA synthesis on stimulation with anti-mu or PMA), proliferation (DNA synthesis on stimulation with anti-mu plus B cell growth factor [BCGF], phorbol myristate acetate [PMA], or Staphylococcus aureus Cowan I [SAC] strain bacteria) and differentiation (Ig synthesis stimulated by T cell replacing factor [TRF]). B-cell maturation-associated cell surface markers were simultaneously investigated. “Early” (less than 10 months) posttransplant patients demonstrated defective B-cell activation and also failed to undergo normal proliferation and differentiation. Despite their functional impairment, the early patients' B cells displayed an “activated” phenotype with increased proportions of B cells displaying CD23 (a BCGF receptor) and decreased proportions of Leu 8+ B cells. Furthermore, these patients were uniquely distinguished by the fact that their B cells only weakly (if at all) expressed the CD19 antigen. In contrast, B cells from “late” patients (greater than or equal to 10 months post-BMT) activated and proliferated normally and displayed a normal cell surface phenotype, yet were unable to differentiate to high rate Ig secretion with TRF. Our results suggest a phenotype/function dissociation in early posttransplant period. With time, B cells in BMT patients acquire a normal surface phenotype and can activate and proliferate normally, yet still demonstrate a block in terminal differentiation.

Engraftment and development of human T and B cells in mice after bone marrow transplantation

Science ◽  
1991 ◽  
Vol 252 (5004) ◽  
pp. 427-431 ◽  
Author(s):  
I Lubin ◽  
Y Faktorowich ◽  
T Lapidot ◽  
Y Gan ◽  
Z Eshhar ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
B Cells ◽  
Marrow Transplantation ◽  
T And B Cells

scholarly journals Tolerogenic interactions between CD8+ dendritic cells and NKT cells prevent rejection of bone marrow and organ grafts

Blood ◽  
2017 ◽  
Vol 129 (12) ◽  
pp. 1718-1728 ◽  
Author(s):  
David Hongo ◽  
Xiaobin Tang ◽  
Xiangyue Zhang ◽  
Edgar G. Engleman ◽  
Samuel Strober
Keyword(s):  
Bone Marrow ◽  
Dendritic Cells ◽  
Bone Marrow Transplantation ◽  
Marrow Transplantation ◽  
Nkt Cells ◽  
Cell Interaction ◽  
Nkt Cell ◽  
Total Lymphoid Irradiation ◽  
Key Points

Key Points Tolerance after bone marrow transplantation requires CD8+ DCs and NKT-cell interaction. CD8+ DCs and NKT cells become tolerogenic after conditioning with total lymphoid irradiation.

scholarly journals Exogenous antigens gain access to the major histocompatibility complex class I processing pathway in B cells by receptor-mediated uptake.

1996 ◽  
Vol 184 (3) ◽  
pp. 1179-1184 ◽  
Author(s):  
Y Ke ◽  
J A Kapp
Keyword(s):  
Dendritic Cells ◽  
Major Histocompatibility Complex ◽  
B Cells ◽  
Major Histocompatibility Complex Class ◽  
Class I ◽  
Complex Class ◽  
Receptor Mediated Endocytosis ◽  
Histocompatibility Complex ◽  
Antigen Presenting ◽  
Gain Access

Professional antigen-presenting cells, such as macrophages, dendritic cells, or B cells, take up soluble, exogenous antigens (Ags) and process them through the class II pathway. Several reports have shown that phagocytic macrophages also process particulate or soluble forms of exogenous Ag via the class I pathway. By contrast, B cells normally do not process soluble, exogenous Ag by way of the class I pathway unless Ags are directly introduced into the cytoplasm. Here we report that B cells present exogenous Ag via the class I pathway when Ags are taken up by receptor-mediated endocytosis. Thus, specialized methods of Ag uptake such as phagocytosis or receptor-mediated endocytosis deliver exogenous Ag into the class I pathway of Ag processing and presentation.

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