Role of PIR-B in Autoimmune Glomerulonephritis

PIR-B, an inhibitory receptor expressed on murine B cells and myeloid cells, regulates humoral and cellular immune responses via its constitutive binding to the ligand, MHC class I molecules, on the same cells (cis) or on different cells (trans). Although it has been speculated that PIR-B is important for maintaining peripheral tolerance, PIR-B single deficiency does not cause overt autoimmune diseases. Recently, however, the combination of its deficiency with the Fas lpr mutation was found to result in augmented production of autoantibodies such as IgG rheumatoid factor and anti-DNA IgG, leading to glomerulonephritis in mice. Although the precise molecular mechanism for the overall scenario is unclear, PIR-B was found to suppress TLR9-mediated production of naturally autoreactive antibodies by innate B cells or B-1 cells by inhibiting the activation of Bruton's tyrosine kinase. Thus, PIR-B is an important regulator of innate immunity mediated by TLR9 in B-1 cells, which can otherwise provoke autoimmunity when overactivated

Genetic Factors of Low-responsiveness to Hepatitis B Virus Vaccine Confirms the Importance of Human Leukocyte Antigen Class II Types in a Japanese Young Adult Population

We investigated the genetic mechanisms underlying the association between human leukocyte antigen (HLA) types and the immune response to hepatitis B virus (HBV) vaccination in 84 healthy Japanese adults, and found that the HLA-DRB1＊04 and HLA-DQB1＊03 frequencies were higher in the low responders (<10 mIU/ml; n=9, 10.7%) compared to the responders (≥10 mIU/ml, n=75, 89.3%). The combination of DRB1＊04 and DQB1＊03 was associated with a low response to vaccination. The DRB1＊04 and DQB1＊03 haplotypes’ frequencies were significantly higher in the low responders compared to responders. Novel candidate HLA types may be important in Japanese individuals