B cell-expressed CD1d promotes MPL/TDCM lipid emulsion adjuvant effects in polysaccharide vaccines

Abstract

T cell-independent type 2 antigens (TI-2 Ags), such as pneumococcal polysaccharides, elicit weak immunoglobulin G (IgG) responses and are refractive to boosting. Overcoming this challenge is critical for improving vaccines. Previously, we demonstrated a lipid-based adjuvant composed of monophosphoryl lipid A, synthetic cord factor, and squalene significantly boosts primary and secondary IgM and IgG production against polysaccharide Ags. Herein, we show beta-2 microglobulin, but not MHC class II, is essential for adjuvant-induced increases in polysaccharide-specific IgG levels. Furthermore, we demonstrate CD1d expression is essential for optimal adjuvant-induced increases in IgG, but is not required for IgG responses to TI-2 Ags administered without adjuvant, with the exception of the bacterial cell wall polysaccharide component, phosphorylcholine. Adoptive transfer of splenic and peritoneal cells from VHB1-8 transgenic mice into CD1d-/- mice revealed adjuvant-induced increases in NP-Ficoll-specific IgG production by CD1d+/+ transgenic B cells, but not recipient B cells, suggesting B cell-expressed CD1d is critical for adjuvant-induced effects on TI-2 antibody responses. Consistent with this, bone marrow chimera mice with selective CD1d deficiency in B cells demonstrated B cell-expressed CD1d was dispensable for iNKT cell development and maintenance but was required for adjuvant-induced increases in protective levels of polysaccharide- and phosphorylcholine-specific IgG. Notably, both iNKT cells and CD1d crosslinking significantly increased IgG production by B cells coactivated with TI-2 Ag and adjuvant, suggesting iNKT-induced CD1d signaling may promote increased IgG production. In summary, our study reveals B cell-dependent CD1d expression is critical for effectiveness of a potent lipid-based adjuvant in augmenting polysaccharide- and phosphorylcholine-specific IgG responses.

Keywords: B cell; CD1d; adjuvant; antibody; polysaccharide vaccine.