| Autor: |
Weller, Sandra, Sterlin, Delphine, Fadeev, Tatiana, Coignard, Eva, Verge de los Aires, Alba, Goetz, Clara, Fritzen, Rémi, Bahuaud, Mathilde, Batteux, Frederic, Gorochov, Guy, Weill, Jean-Claude, Reynaud, Claude-Agnès |
| Zdroj: |
Science Immunology; 2023, Vol. 8 Issue 79, p1-17, 17p |
| Abstrakt: |
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. Tracing the origin of T-independent responses: T-independent (TI) B cell responses develop without T cell help and are mostly directed against repetitive structures such as surface polysaccharides derived from encapsulated bacteria. Using high throughput BCR repertoire sequencing, Weller et al. studied the B cell subsets contributing to human TI responses in healthy individuals vaccinated with the pneumococcal polysaccharide vaccine Pneumovax. The most expanded plasma cells were clonally related to previously mutated peripheral blood B cell precursors, which included marginal zone B cells and remained stable without acquiring further mutations up to 2 months after vaccination. Antibodies specific to bacterial capsular polysaccharides isolated from vaccine-elicited plasma cells cross-reacted with gut bacterial antigens, supporting a model in which human TI responses mobilize marginal zone B cells that are pre-diversified in gut-associated lymphoid tissues. —CO [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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