Single-cell transcriptomic analysis of B cells reveals new insights into atypical memory B cells in COVID-19.

Here, we performed single-cell RNA sequencing of S1 and receptor binding domain protein-specific B cells from convalescent COVID-19 patients with different clinical manifestations. This study aimed to evaluate the role and developmental pathway of atypical memory B cells (MBCs) in response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The results revealed a proinflammatory signature across B cell subsets associated with disease severity, as evidenced by the upregulation of genes such as GADD45B, MAP3K8, and NFKBIA in critical and severe individuals. Furthermore, the analysis of atypical MBCs suggested a developmental pathway similar to that of conventional MBCs through germinal centers, as indicated by the expression of several genes involved in germinal center processes, including CXCR4, CXCR5, BCL2, and MYC. Additionally, the upregulation of genes characteristic of the immune response in COVID-19, such as ZFP36 and DUSP1, suggested that the differentiation and activation of atypical MBCs may be influenced by exposure to SARS-CoV-2 and that these genes may contribute to the immune response for COVID-19 recovery. Our study contributes to a better understanding of atypical MBCs in COVID-19 and the role of other B cell subsets across different clinical manifestations.