PMID- 28561280
OWN - NLM
STAT- MEDLINE
DCOM- 20170731
LR  - 20170731
IS  - 1365-3083 (Electronic)
IS  - 0300-9475 (Linking)
VI  - 86
IP  - 2
DP  - 2017 Aug
TI  - Anti-FcgammaRIIB (CD32) Antibodies Differentially Modulate Murine FVIII-Specific 
      Recall Response in vitro.
PG  - 91-99
LID - 10.1111/sji.12573 [doi]
AB  - Fc gamma receptors (FcgammaRs) for IgG regulate adaptive immune responses by 
      modulating activating and inhibitory signalling pathways within immune cells. 
      Data from a haemophilia A mouse model demonstrate that genetic deletion or 
      blockade of the inhibitory FcgammaR (CD32) suppresses the formation of 
      antibody-secreting cells (ASCs) in vitro. Mechanisms preventing the 
      FVIII-specific recall response, however, remain unclear. Here, the potential role 
      of CD32 inhibition was studied by differentially modulating receptor activity 
      with selected anti-CD32 monoclonal antibodies (mAbs). Splenocytes from immunized 
      FVIII(-/-) mice were restimulated with FVIII in the absence or presence of 
      different anti-CD32 mAbs over 6 days. At day 6, cytokine release was quantified 
      from cell culture supernatant and the formation of FVIII-specific ASCs assessed. 
      Binding of FVIII-containing immune complexes (F8-ICs) to bone marrow-derived 
      dendritic cells (BMdDCs) was also investigated. The antagonistic CD32 mAb AT128 
      suppressed the formation of FVIII-specific ASCs and reduced secretion of IFN-gamma 
      and IL-10. In contrast, the agonistic mAbs AT130-2 and AT130-5, and their 
      F(ab')(2) fragments, allowed the formation of FVIII-specific ASCs, even though 
      the full IgG of AT130-2 reduced binding of F8-ICs to CD32. Data suggest that 
      an inhibitory signal is transmitted when F8-ICs bind to CD32 and that this signal 
      is required during memory B cell (MBC) activation to support formation of 
      FVIII-specific ASCs. If the inhibitory signal is lacking due to CD32 deletion or 
      blockade with antagonistic anti-CD32 mAbs, FVIII-specific T cell stimulation 
      and ASC formation are suppressed, whereas agonistic stimulation of CD32 restores 
      T cell stimulation and ASC formation.
CI  - (c) 2017 The Foundation for the Scandinavian Journal of Immunology.
FAU - Vollack, N
AU  - Vollack N
AUID- ORCID: 0000-0002-0844-6408
AD  - Department of Haematology, Haemostasis, Oncology and Stem Cell Transplantation, 
      Hannover Medical School, Hannover, Germany.
FAU - Friese, J
AU  - Friese J
AD  - Department of Haematology, Haemostasis, Oncology and Stem Cell Transplantation, 
      Hannover Medical School, Hannover, Germany.
FAU - Bergmann, S
AU  - Bergmann S
AD  - Department of Haematology, Haemostasis, Oncology and Stem Cell Transplantation, 
      Hannover Medical School, Hannover, Germany.
FAU - Cragg, M S
AU  - Cragg MS
AD  - Antibody and Vaccine Group, Cancer Science Unit, Faculty of Medicine, General 
      Hospital, University of Southampton, Southampton, UK.
FAU - Tiede, A
AU  - Tiede A
AD  - Department of Haematology, Haemostasis, Oncology and Stem Cell Transplantation, 
      Hannover Medical School, Hannover, Germany.
FAU - Werwitzke, S
AU  - Werwitzke S
AD  - Department of Haematology, Haemostasis, Oncology and Stem Cell Transplantation, 
      Hannover Medical School, Hannover, Germany.
LA  - eng
PT  - Journal Article
PL  - England
TA  - Scand J Immunol
JT  - Scandinavian journal of immunology
JID - 0323767
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Fcgr2b protein, mouse)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Receptors, IgG)
RN  - 130068-27-8 (Interleukin-10)
RN  - 82115-62-6 (Interferon-gamma)
RN  - 9001-27-8 (Factor VIII)
SB  - IM
MH  - Animals
MH  - Antibodies, Monoclonal/*immunology
MH  - B-Lymphocytes/*immunology/metabolism
MH  - Bone Marrow Cells/immunology/metabolism
MH  - Cells, Cultured
MH  - Dendritic Cells/immunology/metabolism
MH  - Factor VIII/genetics/*immunology/metabolism
MH  - Flow Cytometry
MH  - Immunoglobulin G/immunology
MH  - Immunologic Memory/immunology
MH  - Interferon-gamma/immunology/metabolism
MH  - Interleukin-10/immunology/metabolism
MH  - Lymphocytes/immunology/metabolism
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Receptors, IgG/genetics/*immunology/metabolism
MH  - Spleen/cytology/immunology/metabolism
MH  - Time Factors
EDAT- 2017/06/01 06:00
MHDA- 2017/08/02 06:00
CRDT- 2017/06/01 06:00
PHST- 2017/04/05 00:00 [received]
PHST- 2017/05/18 00:00 [accepted]
PHST- 2017/06/01 06:00 [pubmed]
PHST- 2017/08/02 06:00 [medline]
PHST- 2017/06/01 06:00 [entrez]
AID - 10.1111/sji.12573 [doi]
PST - ppublish
SO  - Scand J Immunol. 2017 Aug;86(2):91-99. doi: 10.1111/sji.12573.