Wiskott-Aldrich syndrome protein plays critical and B-cell-intrinsic roles in the humoral immune memory
【摘要】：Objective: Patients with Wiskott-Aldrich syndrome protein(WASP)-deficiency exhibit severe immunodeficiency, including a lack of long-lasting humoral protection. We need to understand the B cell-intrinsic role of WASP in generating antigen-specific memory B cells and humoral recall responses.Methods: We decected the frequency and numbers of memory B cells and atypical MBCs in WAS patients and healthy controls. We decected the frequency and numbers of memory B cells and antigen specifical germinal center B cells and plasmablast cells in WASKO and WT mice. We used WASKO-WT and WASKO-uMT bone marrow chimera mice to decect the defects of B cells was WASp deficient intrinsic.Results: The number and percentage of isotype-switched CD27+ memory B cells in the patients are significantly lower than those in controls. Furthermore, the peripheral blood of the patients exhibits a substantial increase in atypical memory B cells that resemble B cells expanded in persistent viral and parasite infections. In immunized WASP knockout mice, the percentages of antigen-specific germinal center, isotype-switched memory B cells, and plasmablasts in the spleen all are decreased, while the percentages of total germinal center B cells and plasmablasts are unchanged, compared to wild-type mice. In bone marrow chimera mice, where only B cells lack WASP expression, WASP-deficient B cells show reductions in the antigen-specific germinal center and memory subsets similar to those seen in WASP knockout mice. However, the percentages of total germinal center and isotype-switched B cells in the WASP knockout chimera mice are equivalent to or higher than those in the wild-type chimera.Conclusion: WASP-deficient B cells play a critical and cell-intrinsic role in developing the humoral immune deficiency in WAS.