To B relevant to acute inflammation
The nicely ordered boxes and straight lines decorating our immunology class notes, which defined the responsibilities of innate and adaptive immune cells in the immune response, are now becoming blurred and intertwined. Indeed, the recent contribution of Linc Moldawer (Department of Surgery) and colleagues (JEM vol. 208 no. 8 1673-1682 July 2011) describes an exciting new role for interferon (IFN)-activated B cells in acute inflammation, delineating new territory for these previously thought bystanders to the early immune response. Moldawer and team have contributed an elegant and complete study that defines a new paradigm implicating B cells during acute immune response in sepsis.
Employing an induced sepsis model in conjunction with knock-out mice, Rag1-/- ( adaptive immune cell deficient) and umt-/- (B cell deficient), they demonstrate an early and important role for B cells in the response to sepsis. The activation of B cells, while independent of the Toll-like receptors (TLR), was signaled through the type I IFN receptor. Finally, they demonstrated that a depletion of B cells lead to decreased production of chemokine ligand (CXCL10) and other type I IFN chemokines, which they have previously shown play important roles in stimulating phagocytosis by neutrophils.
This study is now added to the growing evidence that B cells may both enhance and repress the immune reaction, independent of their ability to secrete antibodies. Interestingly, depletion of B cells in the treatment of autoimmune diseases with anti-CD20 (Rituximab), while effective in improving disease severity, does so without the reduction in serum autoantibody titers, suggestive that B cells may be modulating T cell response. The Moldawer report not only stimulates further thought about potential pathways for B cells in autoimmune response, but importantly adds another caution of the potential for B cell depletion to lower one’s response to infection.
Thus this Moldawer paper, like all good papers, gets you excited and thinking. I now wish that I had paid more attention in my immunology classes.
(Note: This paper has also been selected for NATURE Research Highlights entitled The B boyz of sepsis. Nature Reviews Immunology vol 11, 501 August 2011 )
Steve P. Sugrue, Ph.D.
Senior Associate Dean for Research Affairs
College of Medicine