| First Author | Horton HM | Year | 2011 |
| Journal | J Immunol | Volume | 186 |
| Issue | 7 | Pages | 4223-33 |
| PubMed ID | 21357255 | Mgi Jnum | J:170701 |
| Mgi Id | MGI:4947163 | Doi | 10.4049/jimmunol.1003412 |
| Citation | Horton HM, et al. (2011) Antibody-Mediated Coengagement of Fc{gamma}RIIb and B Cell Receptor Complex Suppresses Humoral Immunity in Systemic Lupus Erythematosus. J Immunol 186(7):4223-33 |
| abstractText | Engagement of the low-affinity Ab receptor FcgammaRIIb downregulates B cell activation, and its dysfunction is associated with autoimmunity in mice and humans. We engineered the Fc domain of an anti-human CD19 Ab to bind FcgammaRIIb with high affinity, promoting the coengagement of FcgammaRIIb with the BCR complex. This Ab (XmAb5871) stimulated phosphorylation of the ITIM of FcgammaRIIb and suppressed BCR-induced calcium mobilization, proliferation, and costimulatory molecule expression of human B cells from healthy volunteers and systemic lupus erythematosus (SLE) patients, as well as B cell proliferation induced by LPS, IL-4, or BAFF. XmAb5871 suppressed humoral immunity against tetanus toxoid and reduced serum IgM, IgG, and IgE levels in SCID mice engrafted with SLE or healthy human PBMC. XmAb5871 treatment also increased survival of mice engrafted with PBMC from a unique SLE patient. Unlike anti-CD20 Ab, coengagement of FcgammaRIIb and BCR complex did not promote B cell depletion in human PBMC cultures or in mice. Thus, amplification of the FcgammaRIIb inhibitory pathway in activated B cells may represent a novel B cell-targeted immunosuppressive therapeutic approach for SLE and other autoimmune diseases that should avoid the complications associated with B cell depletion. |
