IgM and IgD B cell receptors differentially respond to endogenous antigens and control B cell fate

To defend an organism against invaders such as viruses and bacteria, cells of the immune system need to recognize and respond to foreign microbes. However, these immune cells must also avoid attacking ‘self’ – for example, the healthy tissues of the body – as this could lead to autoimmune disease. B cells are a type of immune cell that is essential in order to produce antibodies, protective proteins that can identify and defend against a broad range of germs: in addition, certain antibodies can also recognize ‘self’. When a B cell first develops, it places its antibody on its surface and uses this protein as a receptor (termed ‘B cell receptor’) to sense its surroundings. Prior to mounting an immune response, B cells carry two closely related versions of the B cell receptor on their surface: IgM and IgD. Both IgM and IgD perform many of the same roles and can largely substitute for one another. However, B cells that recognize ‘self’ decrease their levels of IgM but keep high amounts of IgD on their surface. It is unclear why this is the case, but one possibility is that IgM and IgD may see ‘self’ differently. To investigate this, Noviski et al. used mice with B cells that only carry either IgM or IgD, and tracked how these cells reacted to molecules from ‘self’ and foreign origins. IgM-only B cells reacted more strongly to ‘self’ molecules than IgD-only cells, which suggests that IgM is more sensitive to ‘self’ than IgD. In fact, in mice which are at risk for an autoimmune disease similar to lupus, deleting the IgM receptor prevented antibodies against ‘self’ from being produced. Therefore, reducing the amount of IgM receptors may be a way to keep B cells that are reactive against ‘self’ from inappropriately attacking the host. Meanwhile, the IgD receptor still allows B cells to mount protective antibody responses against foreign microbes. Future studies are necessary to determine whether these differences between IgM and IgD also exist in humans. If this is the case, blocking the IgM receptor could become a new kind of treatment for certain autoimmune diseases.