We take advantage of standard and state-of-the-art experimental approaches, including high-dimensional flow cytometry, bacterial flow cytometry, B cell receptor gene sequencing, 16S rDNA sequencing, bulk and single cell RNA sequencing, phage immunoprecipitation sequencing, and amplification-cloning-expression of human antibodies to address basic questions related to the biology of antibody responses in health and disease. “Frontline” mucosal and splenic marginal zone B cell responses, including splenic IgM and IgG production, intestinal IgA and IgM production, and nasopharyngeal IgD production, constitute the main focus of our research. We are particularly interested in how innate immune and stromal cells regulate the activation of splenic and mucosal B cells, including the induction of antibody responses to commensal bacteria for the shaping of the mucosal microbiota. Finally, we study primary antibody deficiencies to better understand the factors involved in B cell regulation.