Human Blood IgA⁺ Memory B Cells Differ From IgG⁺ B Cells by Expressing Gut-Homing and Regulatory Markers

IgA is the most produced immunoglobulin by the human body, mainly in secretions, and it exerts an important role in the activation and regulation of the immune system. Despite its importance, the phenotype of circulating IgA⁺ B cells is poorly described. Here, we deeply explored the phenotype of IgA⁺ memory B cells compared with IgG⁺ memory B cells from healthy donors using spectral flow cytometry. A bulk transcriptomic analysis was performed on isolated IgA⁺, IgG⁺ and IgM⁺ memory B cells. IgA2⁺ memory B cells expressed more gut-homing markers (CCR9, CCR10, integrin α4β7) and CD11b, GPR183, whereas IgG⁺ B cells expressed more CXCR3 and VLA4 at the protein level. Three other markers were discriminant: CD43 and PD-L1 were more expressed by IgA⁺ B cells, and CD25 associated with IgG⁺ B cells. The transcriptomic analysis of circulating IgA⁺, IgG⁺ and IgM⁺ memory B cells showed a particular signature of IgA⁺ B cells close to IgG⁺ B cells and highly different from IgM⁺ B cells. The transcription factor RUNX2 was upregulated in IgA+ B cells at the mRNA and protein level. Overall, we showed that IgA⁺ memory B cells in blood carry specific markers that may help to better understand IgA⁺ B cell biology.