B cells and autoimmunity

Abstract

There is a growing appreciation for the role for B cells in autoimmune disorders in which inflammation is driven by T cells, in addition to the well-established role for B cells in autoimmune disorders characterized by pathogenic auto-antibodies. Current information on tolerance checkpoints in B cells, B cell depletion, BAFF blockade, regulatory B cells and clonal ignorance mediated by the SIAE/Siglec pathway will be reviewed.

Figure 1. Receptor editing is a major mechanism of central tolerance in B cells

Immature B cells in the bone marrow that encounter multivalent self antigens revert to the small pre-B stage, continue to rearrange κ and if necessary λ light chain genes and generate newly generated B cells that have a novel light chain that is no longer self-reactive. Immature B cells with novel light chains that are no longer part of a self-reactive B cell receptor, then migrate to the periphery as T1 B cells where they mature into newly generated IgM and IgD expressing recirculating T2 B cells and then into mature recirculating B cells.

Figure 2. A number of tolerance mechanisms prevent mature peripheral B cells from developing into pathogenic class switched and somatically mutated auto-antibody producing B cells

These mechanisms include anergy, clonal deletion, specific inhibition of naïve B cells by Tregs in an MHC class II and CD40L dependent manner, clonal inhibition by the Siglec/SIAE pathway, and inhibition by FcγRIIb.