T-independent Responses to Polysaccharides in Humans Mobilize Marginal Zone B Cells Prediversified Against Gut Bacterial Antigens

Overview

Journal Sci Immunol

Specialty Allergy & Immunology

Date 2023 Jan 27

PMID 36706172

Authors

Sandra Weller

Delphine Sterlin

Tatiana Fadeev

Eva Coignard

Alba Verge de Los Aires

Clara Goetz

Remi Fritzen

Mathilde Bahuaud

Frederic Batteux

Guy Gorochov

Jean-Claude Weill

Claude-Agnes Reynaud

Affiliations

Soon will be listed here.

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, IgGCD27 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.

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