Figure 6.

N-glycan Branching Decouples Endocytosis of Surface TLR and CD19/BCR to Suppress Innate and Promote Adaptive Immunity

Branching in B cells promotes endocytic loss of surface TLR (TLR4 and TLR2) to suppress ligand-induced surface TLR signaling and downstream APC activity in B cells via reductions in MHCII, CD80 over CD86 and pro-inflammatory TNFa, which in turn inhibits B cell-dependent CD4⁺ T_H1/T_H17 differentiation and inflammatory demyelination. Concurrently, branching promotes CD19/BCR surface-retention to drive Ca²⁺ flux and proliferation in response to BCR ligands, thereby promoting adaptive B cell function. While intermediate reductions in branching enhance surface TLR signaling, CD19/BCR surface expression/signaling is not impacted. Rather, complete absence of branched N-glycans is required to drive CD19 endocytosis and inhibit BCR responses. Thus, the impact of branching on TLR/APC activity occurs over a large continuum, whereas a minimal level of branching is sufficient to promote BCR responses. Figure created with Biorender.com.