MZ B-cells at the crossroad between BcR-dependent and CD1d-dependent B-cell responses to lipid antigens. Through the expression of LDL-R, MZ B-cells capture and internalize aliprotein E (ApoE)-bound lipid Ags. Dendritic cells and macrophages in tissues secrete ApoE, which is present at low levels in human serum. ApoE-lipid Ag complexes are directed into the endosomal-lysosomal pathway and charged onto CD1d molecules. Exogenous lipids presented by CD1d interact with the invariant TCR of iNKT. These cognate interactions activate iNKT, which produces cytokines, and provide “innate help” to MZ B-cells. Because this internalisation pathway is independent on BcR, it might enhance humoral responses or induce pathogenic Abs . The LDL-R-CD1d-dependent pathway for lipid Ag uptake by B-cells nevertheless provides a mechanism for the adjuvant effects of αGalCer . Other studies suggest that αGalCer is routed to the endosomal-lysosomal pathway and charged onto CD1d molecules after BcR-mediated uptake of protein Ags linked to αGalCer , while BcR-mediated stimulation of human B-cells rapidly down-modulates CD1d expression .
Garraud et al. BMC Immunology 2012 13:63 doi:10.1186/1471-2172-13-63