The Immunological Organ Environment Dictates the Molecular and Cellular Pathways of Cytotoxic Antibody Activity

Gordan S, Albert H, Danzer H, Lux A, Biburger M, Nimmerjahn F (2019)


Publication Type: Journal article

Publication year: 2019

Journal

Book Volume: 29

Pages Range: 3033-3046.e4

Journal Issue: 10

DOI: 10.1016/j.celrep.2019.10.111

Abstract

Cytotoxic immunoglobulin G antibodies are an essential component of therapeutic approaches aimed at depleting self-reactive or malignant cells. More recent evidence suggests that the tissue in which the target cell resides influences the underlying molecular and cellular pathways responsible for cytotoxic antibody activity. By studying cytotoxic IgG activity directed against natural killer cells in primary and secondary immunological organs, we show that distinct organ-specific effector pathways are responsible for target cell depletion. While in the bone marrow, the classical complement pathway and the high-affinity Fcγ-receptor I expressed on organ-resident macrophages were both involved in removing opsonized target cells; in the spleen and blood, all activating FcγRs but not the classical complement pathway were critical for target cell killing. Our study suggests that future strategies aimed at optimizing overall cytotoxic antibody activity may need to consider organ-specific pathways to achieve a maximal therapeutic effect.

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How to cite

APA:

Gordan, S., Albert, H., Danzer, H., Lux, A., Biburger, M., & Nimmerjahn, F. (2019). The Immunological Organ Environment Dictates the Molecular and Cellular Pathways of Cytotoxic Antibody Activity. Cell Reports, 29(10), 3033-3046.e4. https://dx.doi.org/10.1016/j.celrep.2019.10.111

MLA:

Gordan, Sina, et al. "The Immunological Organ Environment Dictates the Molecular and Cellular Pathways of Cytotoxic Antibody Activity." Cell Reports 29.10 (2019): 3033-3046.e4.

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