Siglec-G is a B-1 cell inhibitory receptor and also controls B cell tolerance.

B cell antigen receptor signaling on B-1 cells is controlled by several inhibitory receptors, including Siglec-G, which is a member of the Siglec (sialic acid-binding immunoglobulin-like lectin) family and inhibits B cell signaling. The inhibitory function of Siglec-G is largely restricted to B-1 cells, as demonstrated by studies of Siglec-G-deficient mice showing a phenotype affecting mostly B-1 cells. Siglec-G-deficient mice show a markedly increased B-1a cell population, enhanced B-1 cell signaling, and a shift in the immunoglobulin repertoire secreted by their B-1 cells. Mouse models have provided evidence that Siglec-G binds to the B cell receptor (BCR) on the B cell surface via interaction with sialic acid ligands. As an inhibitory receptor on B cells, Siglec-G controls B cell tolerance, and deficiency of this protein can increase the severity of autoimmune diseases. Despite its importance on B-1 cells, there is evidence that the control of B cell tolerance by Siglec-G occurs on conventional B-2 cells.