Proteasome inhibition causes apoptosis of normal human plasma cells preventing alloantibody production

D. K. Perry, J. M. Burns, H. S. Pollinger, B. P. Amiot, J. M. Gloor, Gregory James Gores, Mark D Stegall

Research output: Contribution to journalArticle

217 Citations (Scopus)

Abstract

Antibody production by normal plasma cells (PCs) against human leukocyte antigens (HLA) can be a major barrier to successful transplantation. We tested four reagents with possible activity against PCs (rituximab, polyclonal rabbit antithymocyte globulin (rATG), intravenous immunoglobulin (IVIG) and the proteasome inhibitor, bortezomib) to determine their ability to cause apoptosis of human bone marrow-derived PCs and subsequently block IgG secretion in vitro. IVIG, rituximab and rATG all failed to cause apoptosis of PCs and neither rituximab nor rATG blocked antibody production. In contrast, bortezomib treatment led to PC apoptosis and thereby blocked anti-HLA and antitetanus IgG secretion in vitro. Two patients treated with bortezomib for humoral rejection after allogeneic kidney transplantation demonstrated a transient decrease in bone marrow PCs in vivo and persistent alterations in alloantibody specificities. Total IgG levels were unchanged. We conclude that proteasome activity is important for PC longevity and its inhibition may lead to new techniques of controlling antibody production in vivo.

Original languageEnglish (US)
Pages (from-to)201-209
Number of pages9
JournalAmerican Journal of Transplantation
Volume9
Issue number1
DOIs
StatePublished - Jan 2009

Fingerprint

Isoantibodies
Proteasome Endopeptidase Complex
Plasma Cells
Apoptosis
Antilymphocyte Serum
Antibody Formation
Immunoglobulin G
Intravenous Immunoglobulins
HLA Antigens
Rabbits
Proteasome Inhibitors
Homologous Transplantation
Bone Marrow Cells
Kidney Transplantation
Transplantation
Bone Marrow

Keywords

  • Antibody production
  • Plasma cell
  • Proteasome inhibition

ASJC Scopus subject areas

  • Transplantation
  • Immunology and Allergy
  • Pharmacology (medical)

Cite this

Proteasome inhibition causes apoptosis of normal human plasma cells preventing alloantibody production. / Perry, D. K.; Burns, J. M.; Pollinger, H. S.; Amiot, B. P.; Gloor, J. M.; Gores, Gregory James; Stegall, Mark D.

In: American Journal of Transplantation, Vol. 9, No. 1, 01.2009, p. 201-209.

Research output: Contribution to journalArticle

Perry, D. K. ; Burns, J. M. ; Pollinger, H. S. ; Amiot, B. P. ; Gloor, J. M. ; Gores, Gregory James ; Stegall, Mark D. / Proteasome inhibition causes apoptosis of normal human plasma cells preventing alloantibody production. In: American Journal of Transplantation. 2009 ; Vol. 9, No. 1. pp. 201-209.
@article{888dfc0311004789ad4c7364f1a9b5b3,
title = "Proteasome inhibition causes apoptosis of normal human plasma cells preventing alloantibody production",
abstract = "Antibody production by normal plasma cells (PCs) against human leukocyte antigens (HLA) can be a major barrier to successful transplantation. We tested four reagents with possible activity against PCs (rituximab, polyclonal rabbit antithymocyte globulin (rATG), intravenous immunoglobulin (IVIG) and the proteasome inhibitor, bortezomib) to determine their ability to cause apoptosis of human bone marrow-derived PCs and subsequently block IgG secretion in vitro. IVIG, rituximab and rATG all failed to cause apoptosis of PCs and neither rituximab nor rATG blocked antibody production. In contrast, bortezomib treatment led to PC apoptosis and thereby blocked anti-HLA and antitetanus IgG secretion in vitro. Two patients treated with bortezomib for humoral rejection after allogeneic kidney transplantation demonstrated a transient decrease in bone marrow PCs in vivo and persistent alterations in alloantibody specificities. Total IgG levels were unchanged. We conclude that proteasome activity is important for PC longevity and its inhibition may lead to new techniques of controlling antibody production in vivo.",
keywords = "Antibody production, Plasma cell, Proteasome inhibition",
author = "Perry, {D. K.} and Burns, {J. M.} and Pollinger, {H. S.} and Amiot, {B. P.} and Gloor, {J. M.} and Gores, {Gregory James} and Stegall, {Mark D}",
year = "2009",
month = "1",
doi = "10.1111/j.1600-6143.2008.02461.x",
language = "English (US)",
volume = "9",
pages = "201--209",
journal = "American Journal of Transplantation",
issn = "1600-6135",
publisher = "Wiley-Blackwell",
number = "1",

}

TY - JOUR

T1 - Proteasome inhibition causes apoptosis of normal human plasma cells preventing alloantibody production

AU - Perry, D. K.

AU - Burns, J. M.

AU - Pollinger, H. S.

AU - Amiot, B. P.

AU - Gloor, J. M.

AU - Gores, Gregory James

AU - Stegall, Mark D

PY - 2009/1

Y1 - 2009/1

N2 - Antibody production by normal plasma cells (PCs) against human leukocyte antigens (HLA) can be a major barrier to successful transplantation. We tested four reagents with possible activity against PCs (rituximab, polyclonal rabbit antithymocyte globulin (rATG), intravenous immunoglobulin (IVIG) and the proteasome inhibitor, bortezomib) to determine their ability to cause apoptosis of human bone marrow-derived PCs and subsequently block IgG secretion in vitro. IVIG, rituximab and rATG all failed to cause apoptosis of PCs and neither rituximab nor rATG blocked antibody production. In contrast, bortezomib treatment led to PC apoptosis and thereby blocked anti-HLA and antitetanus IgG secretion in vitro. Two patients treated with bortezomib for humoral rejection after allogeneic kidney transplantation demonstrated a transient decrease in bone marrow PCs in vivo and persistent alterations in alloantibody specificities. Total IgG levels were unchanged. We conclude that proteasome activity is important for PC longevity and its inhibition may lead to new techniques of controlling antibody production in vivo.

AB - Antibody production by normal plasma cells (PCs) against human leukocyte antigens (HLA) can be a major barrier to successful transplantation. We tested four reagents with possible activity against PCs (rituximab, polyclonal rabbit antithymocyte globulin (rATG), intravenous immunoglobulin (IVIG) and the proteasome inhibitor, bortezomib) to determine their ability to cause apoptosis of human bone marrow-derived PCs and subsequently block IgG secretion in vitro. IVIG, rituximab and rATG all failed to cause apoptosis of PCs and neither rituximab nor rATG blocked antibody production. In contrast, bortezomib treatment led to PC apoptosis and thereby blocked anti-HLA and antitetanus IgG secretion in vitro. Two patients treated with bortezomib for humoral rejection after allogeneic kidney transplantation demonstrated a transient decrease in bone marrow PCs in vivo and persistent alterations in alloantibody specificities. Total IgG levels were unchanged. We conclude that proteasome activity is important for PC longevity and its inhibition may lead to new techniques of controlling antibody production in vivo.

KW - Antibody production

KW - Plasma cell

KW - Proteasome inhibition

UR - http://www.scopus.com/inward/record.url?scp=58049200722&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=58049200722&partnerID=8YFLogxK

U2 - 10.1111/j.1600-6143.2008.02461.x

DO - 10.1111/j.1600-6143.2008.02461.x

M3 - Article

C2 - 18976291

AN - SCOPUS:58049200722

VL - 9

SP - 201

EP - 209

JO - American Journal of Transplantation

JF - American Journal of Transplantation

SN - 1600-6135

IS - 1

ER -