Expansion of an FCRL5+ B cell subset resembling atypical memory B cells in an animal model of malaria

Background: In human malaria, parasites of the genus Plasmodium elicit expansion of atypical memory B cells (atMBCs), which lack the classical markers CD21 and CD27. We have identified a putative population of analogous B cells in a murine model of infection with P. chabaudi, delineated by the marker FCRL5. We performed RNA-Seq on FCRL5+ and FCRL5- B cells sorted from infected mice, so as to characterize the transcriptional profile of these cells and permit comparison to atMBCs in humans. Results: FCRL5+ B cells were found to have distinct transcriptional profiles from FCRL5- B cells, with approximately 400 genes exhibiting significant differences between the two groups. Additionally, about 25% of these differentially expressed genes were also differentially expressed in human atMBCs versus classical MBCs, as previously described by Sullivan et al (PLoS Pathogens 2015). Conclusions: FCRL5+ class-switched B cells are a transcriptionally distinct subset arising in P. chabaudi infection, with transcriptional similarities to human atMBCs that develop in chronic malaria settings. Class-switched B cells (IgM- IgD- CD19+) were isolated into FCRL5+ and FCRL5- populations by double-sorting from the blood of C57BL/6 adult female mice 21 days post-infection with Plasmodium chabaudi. Pools of ~1000 cells were isolated and processed for RNA sequencing. 5 biological replicates were analyzed for each sample type.