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Sequential class switching generates antigen-specific gut IgA from IgG1 B cells.

Emily R Siniscalco1, Hailong Meng2, Gisela Gabernet2

  • 1Department of Immunobiology, Yale School of Medicine, New Haven, CT 06520, USA; Center for Human Immunobiology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.

Immunity
|November 18, 2025
PubMed
Summary
This summary is machine-generated.

Immunoglobulin A (IgA) is crucial for gut immunity. This study reveals that IgG1 B cells can generate IgA, suggesting a sequential class-switching pathway for mucosal immunity and informing the development of new vaccines.

Keywords:
B cellBCR sequencingIgAPeyer's patchaffinity maturationclass switch recombinationgerminal centersgut immunitymucosal vaccinationplasma cell

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Area of Science:

  • Immunology
  • Microbiology
  • Vaccinology

Background:

  • Immunoglobulin A (IgA) is the main antibody isotype protecting the intestinal barrier.
  • The precise mechanisms of antigen-specific IgA induction in the gut remain largely unknown.
  • Gut-associated lymphoid tissues possess unique structural and functional characteristics.

Purpose of the Study:

  • To elucidate the fundamental pathways of antigen-specific IgA induction in the gut.
  • To investigate the role of germinal center (GC) and non-GC pathways in IgA B cell generation.
  • To explore the potential for sequential class switching in IgA production.

Main Methods:

  • Analysis of B cell populations in gut lymphoid organs.
  • Tracking of antibody class switching and affinity maturation.
  • Comparative studies in mouse models and human tissues.

Main Results:

  • Demonstrated the generation of affinity-matured IgA B cells via both GC and nonGC pathways.
  • Discovered that IgG1 GC B cells can produce gut mucosal IgA in mice.
  • Identified a similar IgG1-IgA relationship in human mucosal and non-mucosal sites.
  • Proposed a model of sequential class switching linking mucosal IgA and systemic IgG1.

Conclusions:

  • Gut IgA induction involves noncanonical pathways, including sequential class switching from IgG1.
  • Understanding these pathways is critical for designing effective mucosal vaccines.
  • This research bridges the understanding of humoral immunity in mucosal and systemic compartments.