How B cells shape the immune response against Mycobacterium tuberculosis

Abstract

Extensive work illustrating the importance of cellular immune mechanisms for protection against Mycobacterium tuberculosis has largely relegated B-cell biology to an afterthought within the tuberculosis (TB) field. However, recent studies have illustrated that B lymphocytes, through a variety of interactions with the cellular immune response, play previously underappreciated roles in shaping host defense against non-viral intracellular pathogens, including M. tuberculosis. Work in our laboratory has recently shown that, by considering these lymphocytes more broadly within their variety of interactions with cellular immunity, B cells have a significant impact on the outcome of airborne challenge with M. tuberculosis as well as the resultant inflammatory response. In this review, we advocate for a revised view of TB immunology in which roles of cellular and humoral immunity are not mutually exclusive. In the context of our current understanding of host defense against non-viral intracellular infections, we review recent data supporting a more significant role of B cells during M. tuberculosis infection than previously thought.

Figure 1. Schematic of how B cells shape the immune response against M. tuberculosis

B cells modulate the murine host response against M. tuberculosis in a variety of ways. Upon acute infection, selective engagement of stimulatory Fcγ receptors by antibody complexes heightens the Th1 response and promotes mycobacterial containment with minimal inflammation. Conversely, engagement of inhibitory FcγRIIB increases IL-10 production and compromises immunity against M. tuberculosis. Interestingly, an immunosuppressive phenotype in the absence of B cells subverts optimal containment of acute M. tuberculosis challenge initially, but delays inflammatory progression during chronic TB.