Development and characterisation of monoclonal antibodies specific for the murine inhibitory FcγRIIB (CD32B)

Emily L Williams, Alison L Tutt, Ruth R French, H T Claude Chan, Betty Lau, Christine A Penfold, C Ian Mockridge, Ali Roghanian, Kerry L Cox, J Sjef Verbeek, Martin J Glennie, Mark S Cragg

Research output: Contribution to journalArticle (Academic Journal)peer-review

26 Citations (Scopus)

Abstract

Fc receptors (FcRs) play a key role in regulating and coordinating responses from both innate and adaptive arms of the immune system. The inhibitory Fc gamma receptor II (FcγRIIB; CD32) is central to this regulation with FcγRIIB(-/-) mice demonstrating augmented responses to mAb immunotherapy, elevated incidence and severity of auto-immunity, and increased response to mAb-mediated cancer therapy. To date, these observations have remained unexploited therapeutically, partly through a lack of specific mAb reagents capable of exclusively binding mouse FcγRIIB. Thus almost all of the FcγRIIB-binding mAb currently available, such as 2.4G2, also bind FcγRIII (CD16), and polyclonal reagents have limited availability and are of unproven specificity and avidity, making in vivo manipulation of FcγRIIB impossible. Following an extensive immunisation protocol using FcγRIIB(-/-) mice, we recently produced three unique mAb that are suitable for this purpose. Here we characterise these novel reagents and demonstrate that they fall into two distinct categories; those which cause phosphorylation and subsequent activation of FcγRIIB (agonistic) and those that block receptor phosphorylation (antagonistic). These two types of mAb exhibit different characteristics in a range of biochemical, cellular, and functional assays relevant to FcγRIIB activity and mAb therapy.

Original languageEnglish
Pages (from-to)2109-20
Number of pages12
JournalEuropean Journal of Immunology
Volume42
Issue number8
DOIs
Publication statusPublished - Aug 2012

Keywords

  • Animals
  • Antibodies, Monoclonal
  • Cell Death
  • Cells, Cultured
  • Immunotherapy
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Phosphorylation
  • Receptors, IgG

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