Suppression of autoimmunity by B lymphocyte membrane protein CD72

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C-type lectin-like domain (CTLD) of B cell membrane protein CD72 is suggested to associated with development of autoimmune diseases. However, the glycan ligand and function of its CTLD is not clear. In this study, some kinds of sulfated glycans were identified as CD72 ligands by glycan array screening using CD72 recombinant protein.Interestingly, some of the identified CD72 ligands are autoimmune disease-associated antigens. In addition, the effect of CD72 ligand on B cell antigen receptor (BCR) signaling in primary B cells from QM mice and QM CD72 deficient mice by analyzing calcium influx using NP-conjugated CD72 ligand and NP-conjugated BSA, showed CD72-dependent reduction of BCR signaling following ligation of CD72 ligand-containing antigen. Moreover, the amount of serum anti-CD72 ligand IgM classantibody was increased in C57BL/6 CD72 deficient mice compared with that in C57BL/6 mice. These results suggest novel self and non-self recognition mechanism of B cells by CD72-CD72 ligand interaction-mediated suppression of BCR signaling and antibody production against CD72 ligand-containing antigens.