Disrupting CD22-cis-ligand interactions ameliorates type 1 diabetes and graft rejection by expanding regulatory B cells

CD22 is an inhibitory receptor expressed in B cells and is constitutively associated with α2,6-sialylated membrane proteins expressed on the same cell (cis-ligands). However, interaction with cis-ligands is required for the function of CD22 only in part. To address the role of ligand interaction of CD22 in immune responses, here we generated anti-CD22 antibody 1C5 that specifically inhibits ligand binding of CD22. Both Cd22−/− mice and mice treated with 1C5 show expansion of regulatory B (Breg) cells in follicular (FO) B cells, suggesting a crucial role of ligand interaction of CD22 in inhibiting the expansion of FO Breg cells. CD22 appears to recognize BCR and TLRs thereby directly or indirectly suppressing TLR signaling essential for expansion of Breg cells. Treatment of mice with 1C5 ameliorates skin graft rejection and type 1 diabetes with expansion of regulatory γδ T cells probably through expansion of Breg cells, suggesting ligand interaction of CD22 as a novel target of therapy for autoim mune diseases and graft rejection.