WAS Protein Deficiency Disrupts Memory B Cell Formation During Acute LCMV Infection

Wiskott-Aldrich syndrome (WAS) is a rare x-linked monogenic immunodeficiency disease, caused by the mutation of WAS gene encoding WAS protein (WASp). Previous findings in WAS patients show B cell perturbations in the periphery, characterized by diminished B-cell numbers and phenotype abnormalities, including reduced frequency of classical CD27 + memory B cells (MBCs), accompanied by an unusual expansion of atypical CD21low MBCs. The mechanism underlying these abnormalities in MBCs developmental pathway has not been completely dissected. In this study, WASp knock-out mice undergone with acute lymphocytic choriomeningitis virus (LCMV) infection was used as a model to investigate the effects of WASp deficiency on the differentiation of MBCs and the possible mechanisms. We found that by day 11 after infection, the proportion of classical IgG2c + MBCs was dramatically decreased, this was accompanied by a corresponding increase in the proportion of atypical CD21low MBCs. Using single-cell RNA sequencing (scRNA-seq), we also identified WASp deficiency promoted the formation of atypical MBCs during acute viral infection. Remarkably, our study revealed a marked reduction of WASp expression in atypical MBCs. Overall, our data show that WASp is differentially expressed in MBCs subsets, and manipulates the fate of MBCs during acute LCMV infection.