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

ABSTRACT: Immunoglobulin (Ig)A is the primary isotype protecting the gut barrier, yet fundamental aspects of antigen-specific IgA induction remain unknown. Gut lymphoid organs are chronically exposed to foreign antigens, are structurally different from other lymphoid tissues, and are functionally unique. This suggests gut IgA induction occurs through noncanonical means. Indeed, we observed the generation of affinity-matured IgA B cells through both germinal center (GC) and nonGC pathways. Although most antibody isotypes are generated directly from naive IgM B cells, we discovered that IgG1 GC B cells can generate gut mucosal IgA in mice, with a similar relationship in mucosal and non-mucosal sites in humans. This supports a model of IgA generation through sequential class switching, linking the spec

SUBMITTER: Siniscalco ER 

PROVIDER: S-EPMC12834128 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature