i27-Breg: Discovery of a New Anti-inflammatory B Cell

Article: NIH scientists discover new B cell that tempers autoimmunity
Source: National Eye Institute
Published: December 2, 2021 

i27-Breg infusion successfully treated induced uveitis in mice (top).
IL-27 receptor is necessary for therapeutic effect (bottom).

Scientists at the National Eye Institute have discovered a new type of B cell that tempers the immune system, thereby reducing chronic inflammation in autoimmune diseases. Termed regulatory B cells (Bregs), these cells represent a small population of B cells that are derived from plasma blasts or plasma cells; although similar to other Bregs, the newly discovered cells express a distinct genetic profile of innate B-1a cell lineage. Bregs patrol the blood and function in modulating the immune system through expression of anti-inflammatory cytokines (e.g., IL-10 and IL-35) that counterbalance the physiological effects of pro-inflammatory cytokines (e.g., IFN-gamma and IL-17). A balance between pro- and anti-inflammatory cytokines is essential to a healthy immune system, one that can mount a robust response against pathogens while not reacting excessively to self-cells, as in autoimmune disease. In lab tests in mice, purified infusion of i27-Breg suppressed autoimmune uveitis (and encephalomyelitis) through "up-regulation of inhibitory receptors (Lag3, PD-1), suppression of T-cell (Th17/Th1) responses, and propagation of inhibitory signals that converted conventional B cells to regulatory lymphocytes that secrete IL-10 and/or IL-35 in eye, brain, and spinal cord." Unlike i35-Breg, a similar Breg also discovered by these researchers, i27-Breg demonstrated a quicker response to suppress autoimmune uveitis and MS-like disease. i27-Breg also has an advantage of being able to proliferate to sustain IL-27 secretion in vivo, suggesting that it may have greater therapeutic potential over biologics (IL-10 or IL-35), which are rapidly cleared by the body. Notably, IL-27 receptor is necessary for any therapeutic effect, as i27-Breg infusions into mice lacking the IL-27 receptor failed to attenuate disease symptoms. Finally, because i27-Breg is neither antigen-specific nor disease-specific, the researchers point out that it could be effective immunotherapy for a wide range of autoimmune diseases. They are currently working on the use of exosomes (extracellular vesicles) as a vector to deliver lab-grown IL-27 into the body, which they acknowledge is less technically challenging than producing Breg cells in the lab.

My rating of this study: ⭐⭐⭐

Choi JK, Yu C, Bing SJ, et al. "IL-27-producing B-1a cells suppress neuroinflammation and CNS autoimmune diseases." PNAS.  118(47):e2109548118. 23 November 2021. https://doi.org/10.1073/pnas.2109548118