B CELLS Constant Anergy Signal

Anergy is a process by which autoreactive immune cells are rendered incapable of responding to self-antigens. Gauld et al. use the Ars/A1 mouse to tackle the question of whether B cell anergy can be induced by a single transient encounter with a self-antigen or whether it requires a more continuous interaction between the receptor and the antigen. B cells of the Ars/A1 mouse are engineered to recognize arsonate but can also become anergic in response to binding to a low-affinity self-antigen. Anergy is inhibited by arsonate-tyrosine (ArsTyr), which is monovalent and competes with the self-antigen for the B cell receptor (BCR). Because it is monovalent, ArsTyr cannot stimulate the BCR. Ars/A1 B cells exhibit increased basal intracellular calcium concentration and increased phosphorylation of extracellular signal-regulated kinase (ERK), both of which were reversed by exposure of the cells to ArsTyr, which displaced the self-antigen. Furthermore, ArsTyr also extended the life span of the Ars/A1 B cells. ArsTyr also partially restored the response--calcium mobilization and increased CD86 abundance--of the Ars/A1 B cells to antibodies against immunoglobulin M (IgM). Thus, anergy is reversible and appears to require constant binding of the self-antigen to maintain the unresponsive state.

S. B. Gauld, R. J. Benschop, K. T. Merrell, J. C. Cambier, Maintenance of B cell anergy requires constant antigen receptor occupancy and signaling. Nat. Immunol. 6, 1160-1167 (2005). [PubMed]