CD6 Receptor Regulates Intestinal Ischemia/Reperfusion-induced Injury by Modulating Natural IgM-producing B1a Cell Self-renewal.

Intestinal ischemia/reperfusion (I/R) injury is a relatively common pathological condition that can lead to multi-organ failure and mortality. Regulatory mechanism for this disease is poorly understood, although it is established that circulating pathogenic natural IgM, which is primarily produced by B1a cells outside of the peritoneal cavity, are integrally involved. CD6 was originally identified as a marker for T cells and was later found to be present on some subsets of B cells in humans; however, whether CD6 plays any role in intestinal I/R-induced injury and, if so, the underlying mechanisms, remain unknown. Here we report that CD6^-/- mice were significantly protected from intestinal inflammation and mucosal damage compared with WT mice in a model of intestinal I/R-induced injury. Mechanistically, we found that CD6 was selectively expressed on B1 cells outside of the bone marrow and peritoneal cavity and that pathogenic natural IgM titers were reduced in the CD6^-/- mice in association with significantly decreased B1a cell population. Our results reveal an unexpected role of CD6 in the pathogenesis of intestinal IR-induced injury by regulating the self-renewal of B1a cells.

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