A Humanized Mouse Identifies the Bone Marrow as a Niche with Low Therapeutic IgG Activity

被引：41

作者：

Lux, Anja ^{[1
]}

Seeling, Michaela ^{[1
]}

Baerenwaldt, Anne ^{[1
]}

Lehmann, Birgit ^{[1
]}

Schwab, Inessa ^{[1
]}

Repp, Roland ^{[2
]}

Meidenbauer, Norbert ^{[3
]}

Mackensen, Andreas ^{[3
]}

Hartmann, Arndt ^{[4
]}

Heidkamp, Gordon ^{[5
]}

Dudziak, Diana ^{[5
]}

Nimmerjahn, Falk ^{[1
]}

机构：

[1] Univ Erlangen Nurnberg, Inst Genet, Dept Biol, D-91058 Erlangen, Germany

[2] Klinikum Bruderwald, Med Dept 5, D-96049 Bamberg, Germany

[3] Univ Hosp Erlangen, Dept Internal Med Hematol Oncol 5, D-91054 Erlangen, Germany

[4] Univ Hosp Erlangen, Dept Pathol, D-91054 Erlangen, Germany

[5] Univ Hosp Erlangen, Dept Dermatol, D-91052 Erlangen, Germany

来源：

CELL REPORTS | 2014年 / 7卷 / 01期

关键词：

FC-GAMMA-RIV; ANTI-CD20; MONOCLONAL-ANTIBODY; C-RECEPTOR POLYMORPHISMS; HUMAN IMMUNE-SYSTEM; IN-VIVO; LIVER METASTASES; B-LYMPHOCYTES; MICE; IMMUNOTHERAPY; DEPLETION;

D O I：

10.1016/j.celrep.2014.02.041

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Genetic differences between humans and in vivo model systems, including mice and nonhuman primates, make it difficult to predict the efficacy of immunoglobulin G (IgG) activity in humans and understand the molecular and cellular mechanisms underlying that activity. To bridge this gap, we established a small-animal model system that allowed us to study human IgG effector functions in the context of an intact human immune system without the interference of murine Fc gamma receptors expressed on mouse innate immune effector cells in vivo. Using a model of B cell depletion with different human IgG variants that recognize CD20, we show that this humanized mouse model can provide unique insights into the mechanism of human IgG activity in vivo. Importantly, these studies identify the bone marrow as a niche with low therapeutic IgG activity.

引用

页码：236 / 248

页数：13

共 59 条

[1] Fcγ receptor IIB (FcγRIIB) maintains humoral tolerance in the human immune system in vivo [J].

Baerenwaldt, Anne ;

Lux, Anja ;

Danzer, Heike ;

Spriewald, Bernd M. ;

Ullrich, Evelyn ;

Heidkamp, Gordon ;

Dudziak, Diana ;

Nimmerjahn, Falk .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2011, 108 (46) :18772-18777

[2] Differential contribution of three activating IgG Fc receptors (FcγRI, FcyRIII, and FcγRIV) to IgG2a- and IgG2b-induced autoimmune hemolytic anemia in mice [J].

Baudino, Lucie ;

Nimmerjahn, Falk ;

da Silveira, Samareh Azeredo ;

Martinez-Soria, Eduardo ;

Saito, Takashi ;

Carroll, Michael ;

Ravetch, Jeffrey V. ;

Verbeek, J. Sjef ;

Izui, Shozo .

JOURNAL OF IMMUNOLOGY, 2008, 180 (03) :1948-1953

[3] Type II (tositumomab) anti-CD20 monoclonal antibody out performs type I (rituximab-like) reagents in B-cell depletion regardless of complement activation [J].

Beers, Stephen A. ;

Chan, Claude H. T. ;

James, Sonya ;

French, Ruth R. ;

Attfield, Kathrine E. ;

Brennan, Claire M. ;

Ahuja, Anupama ;

Shlomchik, Mark J. ;

Cragg, Mark S. ;

Glennie, Martin J. .

BLOOD, 2008, 112 (10) :4170-4177

[4] Antigenic modulation limits the efficacy of anti-CD20 antibodies: implications for antibody selection [J].

Beers, Stephen A. ;

French, Ruth R. ;

Chan, H. T. Claude ;

Lim, Sean H. ;

Jarrett, Timothy C. ;

Vidal, Regina Mora ;

Wijayaweera, Sahan S. ;

Dixon, Sandra V. ;

Kim, Hyungjin ;

Cox, Kerry L. ;

Kerr, Jonathan P. ;

Johnston, David A. ;

Johnson, Peter W. M. ;

Verbeek, J. Sjef ;

Glennie, Martin J. ;

Cragg, Mark S. .

BLOOD, 2010, 115 (25) :5191-5201

[5] Low level of FcγRIII expression on murine natural killer cells [J].

Biburger, Markus ;

Nimmerjahn, Falk .

IMMUNOLOGY LETTERS, 2012, 143 (01) :53-59

[6] Monocyte Subsets Responsible for Immunoglobulin G-Dependent Effector Functions In Vivo [J].

Biburger, Markus ;

Aschermann, Susanne ;

Schwab, Inessa ;

Lux, Anja ;

Albert, Heike ;

Danzer, Heike ;

Woigk, Melissa ;

Dudziak, Diana ;

Nimmerjahn, Falk .

IMMUNITY, 2011, 35 (06) :932-944

[7] Development of human lymphoid cells [J].

Blom, Blanca ;

Spits, Hergen .

ANNUAL REVIEW OF IMMUNOLOGY, 2006, 24 :287-320

[8] 'Rituximab-induced inhibition of antiapoptotic cell survival pathways: implications in chemo/immunoresistance, rituximab unresponsiveness, prognostic and novel therapeutic interventions' [J].

Bonavida, B. .

ONCOGENE, 2007, 26 (25) :3629-3636

[9] Specificity and affinity of human Fcγ receptors and their polymorphic variants for human IgG subclasses [J].

Bruhns, Pierre ;

Iannascoli, Bruno ;

England, Patrick ;

Mancardi, David A. ;

Fernandez, Nadine ;

Jorieux, Sylvie ;

Daeron, Marc .

BLOOD, 2009, 113 (16) :3716-3725

[10] Potent antibody therapeutics by design [J].

Carter, PJ .

NATURE REVIEWS IMMUNOLOGY, 2006, 6 (05) :343-357

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