![]() Early in development, B cells randomly rearrange their immunoglobulin genes through VDJ recombination and encounter a series of tolerance checkpoints that serve to remove autoreactive B cell receptors (BCRs) from the repertoire. The pre-immune mature naïve B cell compartment must balance the need for a diverse antibody repertoire with the risk of autoantibody-mediated disease. If this is the case, blocking the IgM receptor could become a new kind of treatment for certain autoimmune diseases. Meanwhile, the IgD receptor still allows B cells to mount protective antibody responses against foreign microbes.įuture studies are necessary to determine whether these differences between IgM and IgD also exist in humans. 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. 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. 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. 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. It is unclear why this is the case, but one possibility is that IgM and IgD may see ‘self’ differently. However, B cells that recognize ‘self’ decrease their levels of IgM but keep high amounts of IgD on their surface. Both IgM and IgD perform many of the same roles and can largely substitute for one another. Prior to mounting an immune response, B cells carry two closely related versions of the B cell receptor on their surface: IgM and IgD. 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. However, these immune cells must also avoid attacking ‘self’ – for example, the healthy tissues of the body – as this could lead to autoimmune disease.ī 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’. To defend an organism against invaders such as viruses and bacteria, cells of the immune system need to recognize and respond to foreign microbes. We propose a role for IgD in maintaining the quiescence of autoreactive B cells and restricting their differentiation into autoantibody secreting cells. Similarly, IgD-only B cells generate normal germinal center, but impaired IgG1 + SLPC responses to T-dependent immunization. IgD-only Lyn −/− B cells cannot generate autoantibodies and short-lived plasma cells (SLPCs) in vivo, a fate thought to be driven by intense BCR signaling induced by endogenous antigens. Despite signaling strongly in vitro, IgD is less sensitive than IgM to endogenous antigen in vivo and developmental fate decisions are skewed accordingly. We introduced the Nur77-eGFP reporter of BCR signaling into mice that express each BCR isotype alone. Because these isotypes are presumed to be redundant, it is unknown how this could impose tolerance. IgM but not IgD is downregulated on autoreactive B cells. Naive B cells co-express two BCR isotypes, IgM and IgD, with identical antigen-binding domains but distinct constant regions.
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