T-independent responses to polysaccharides in humans mobilize marginal zone B cells prediversified against gut bacterial antigens
Sandra Weller, Delphine Sterlin, Tatiana Fadeev, Eva Coignard, Alba Verge de los Aires, Clara Goetz, Rémi Fritzen, Mathilde Bahuaud, Frédéric Batteux, Guy Gorochov, Jean–Claude Weill, Claude–Agnès Reynaud
Abstract
Marginal zone (MZ) B cells are one of the main actors of T-independent (TI) responses in mice. To identify the B cell subset(s) involved in such responses in humans, we vaccinated healthy individuals with Pneumovax, a model TI vaccine. By high-throughput repertoire sequencing of plasma cells (PCs) isolated 7 days after vaccination and of different B cell subpopulations before and after vaccination, we show that the PC response mobilizes large clones systematically, including an immunoglobulin M component, whose diversification and amplification predated the pneumococcal vaccination. These clones could be mainly traced back to MZ B cells, together with clonally related IgA + and, to a lesser extent, IgG + CD27 + B cells. Recombinant monoclonal antibodies isolated from large PC clones recognized a wide array of bacterial species from the gut flora, indicating that TI responses in humans largely mobilize MZ and switched B cells that most likely prediversified during mucosal immune responses against bacterial antigens and acquired pneumococcal cross-reactivity through somatic hypermutation.