Suppression of innate and adaptive B cell activation pathways by antibody coengagement of FcgammaRIIb and CD19.

Szili, Dániel and Cserhalmi, Marcell and Banko, Zsuzsanna and Nagy, György and Szymkowski, David E. and Sármay, Gabriella (2014) Suppression of innate and adaptive B cell activation pathways by antibody coengagement of FcgammaRIIb and CD19. MABS, 6 (4). pp. 991-999. ISSN 1942-0862

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Abstract

The Fc receptor (FcgammaRIIb) inhibits B cell responses when coengaged with B cell receptor (BCR), and has become a target for new autoimmune disease therapeutics. For example, BCR and FcgammaRIIb coengagement via the Fc-engineered anti-CD19 XmAb5871 suppresses humoral immune responses. We now assess effects of XmAb5871 on other activation pathways, including the pathogen-associated molecular pattern receptor, TLR9. Since TLR9 signaling is implicated in autoimmune diseases, we asked if XmAb5871 could inhibit TLR9 costimulation. We show that XmAb5871 decreases ERK and AKT activation, cell proliferation, cytokine, and IgG production induced by BCR and/or TLR9 signals. XmAb5871 also inhibited differentiation of citrullinated peptide-specific plasma cells from rheumatoid arthritis patients. XmAb5871 may therefore have potential to suppress pathogenic B cells in autoimmune diseases.

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