Research Scientist University of Virginia Charlottesville, Virginia, United States
Disclosure(s):
Claudia Rival, PhD: No financial relationships to disclose
Introduction/Rationale: Alpha-gal syndrome (AGS) is acquired through bites from the lone star tick (LST), leading to IgE-mediated reactions to the mammalian oligosaccharide galactose-alpha-1,3-galactose (alpha-gal) present in non-primate mammalian meat and derived products. The mechanisms driving IgE production to alpha-gal are unknown. We previously identified a significant association of CCR6+ memory B cells in the peripheral blood of AGS patients vs healthy controls. Thus, we hypothesized that CCR6 is required for IgE production after tick exposure.
Methods: Wild-type (WT) and CCR6-/- mice were sensitized with LST extract. After 35 days, serum tick-specific IgE and IgG1 levels were measured by ELISA. To assess the B cell-intrinsic requirement for CCR6, muMT mice were reconstituted with purified B cells from WT or CCR6-/- donors prior to sensitization. Splenocytes were stimulated in vitro with anti-CD40 and IL-4 for 5 days, and expression of eGLT, Bcl6, and Blimp1 were quantified by qPCR.
Results: CCR6-/- mice showed a significant reduction in tick-specific IgE without affecting IgG1 responses. Reconstitution of muMT mice with WT but not CCR6-/- B cells restored IgE production after tick sensitization, indicating a B cell-intrinsic role for CCR6. In vitro, CCR6-/- splenocytes showed reduced expression of genes associated with IgE class switching and plasma cell differentiation.
Conclusion: CCR6 expression on B cells is required for IgE production following tick sensitization. Our findings suggest that CCR6 signaling promotes IgE class switching and plasma cell differentiation, providing new mechanistic insight into AGS.
