Hematologic disorder-associated Cxcr4 gain-of-function mutation leads to uncontrolled extrafollicular immune response.

ABSTRACT: The extrafollicular immune response is essential to generate a rapid but transient wave of protective antibodies during infection. Despite its importance, the molecular mechanisms controlling this first response are poorly understood. Here, we demonstrate that enhanced Cxcr4 signaling caused by defective receptor desensitization leads to exacerbated extrafollicular B-cell response. Using a mouse model bearing a gain-of-function mutation of Cxcr4 described in 2 human hematologic disorders, warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome and Waldenström macroglobulinemia, we demonstrated that mutant B cells exhibited enhanced mechanistic target of rapamycin signaling, cycled more, and differentiated more potently into plasma cells than wild-type B cells after Toll

SUBMITTER: Alouche N 

PROVIDER: S-EPMC8176768 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature