STALing B cell responses with CD22

Abstract

Suppressing unwanted humoral immune responses without compromising the host's ability to respond to foreign pathogens is a primary goal for therapies aimed at ameliorating harmful autoantibody production. Global suppression of the immune system via lymphocyte depletion and/or immunosuppressive drugs can have off-target effects, a limitation to conventional therapies. In this issue of the JCI, Macauley and colleagues utilize a novel platform to inhibit antigen-specific antibody production that preserves the immune system's ability to respond to unrelated antigens.

Figure 1. Multiple cellular and molecular targets for modulating Ag-specific B cell responses.

Schematic of methods to achieve Ag-specific vs. nonspecific B cell activation or inhibition. STALs directly induce Ag-specific B cell tolerance by simultaneously targeting Ag to the BCR together with inhibitory signals delivered by CD22 ligands. Alternatively, delivery of Ag to the BCR together with CD180 crosslinking results in Ag-specific B cell activation and Ab production. B cell responses may also be modulated by Ag delivery to receptors found on DC subsets. Ag targeted to SIGLEC-H or BDCA2 found on pDCs indirectly inhibits B cell responses via inhibition of effector CD4⁺ T cell activation, whereas Ag-specific B cell responses can be induced by delivering Ag to certain C-type lectin receptors found on myeloid DCs. B cell responses can be enhanced or inhibited by nonspecific agents such as TLR agonists or immunosuppressive drugs, respectively.