Dependence of surface monoclonal antibody binding on dynamic changes in FcgammaRIIb expression.
Receptors for the Fc region of immunoglobulin G (FcgammaRs) are expressed on a broad range of haematopoietic cell types and are responsible for regulating antibody production and linking the humoral and effector responses. In response to a number of stimuli, such as cytokine signals or inflammation, FcgammaR expression at the cell surface is dynamically regulated. On B cells, we observed what appeared to be a correlation between CD22 expression and FcgammaRIIb expression when the latter was varied in a number of models. Further investigation revealed that this was specific to a particular anti-CD22 monoclonal antibody, which appeared to require stabilization by interaction with FcgammaRIIb for optimal binding to CD22. Since alterations in the regulation of FcgammaR expression are important in controlling immune responses and have been associated with a number of immune-mediated disease states, we suggest that it might be prudent to confirm the expression of cell surface markers by two independent methods. Furthermore, because the efficacy of therapeutic antibodies may depend upon their interaction with FcgammaRs, our results are relevant to their design and assessment.
Walker
Jennifer A
JA
Department of Medicine, Cambridge Institute for Medical Research, Addenbrooke's Hospital, Cambridge, UK. jw425@cam.ac.uk
Smith
Kenneth G C
KG
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism*; D001402:B-Lymphocytes / Q000276:immunology; D016130:Immunophenotyping; D015847:Interleukin-4 / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D017452:Receptors, IgG / Q000172:deficiency / Q000378:metabolism*; D051918:Sialic Acid Binding Ig-like Lectin 2 / Q000378:metabolism
D000911:Antibodies, Monoclonal; C497868:Cd22 protein, mouse; C499172:Fcgr2b protein, mouse; D017452:Receptors, IgG; D051918:Sialic Acid Binding Ig-like Lectin 2; D015847:Interleukin-4