Atypical memory B cells form a pre-plasmacellular reservoir for steady-state IgD responses to common nasopharyngeal antigens

The human nasopharyngeal mucosa includes organized lymphoepithelial structures continually engaged in frontline immune responses to aerodigestive antigens. Advancing our understanding of these responses might lead to the development of new strategies for the prevention and treatment of common immune disorders such as allergies. Here we identified a hitherto elusive tonsillar subset of atypical IgD class-switched IgD+IgM- memory (IgD-ME) B cells that were clonally related to IgD+IgM- germinal center (IgD-GC) B cells and IgD-secreting IgD+IgM- plasma cells (IgD-PCs) but not anergic IgD+IgM- B cells. Consistent with their pre-plasmacellular properties, IgD-ME B cells served as preferential precursors of IgD-PCs over IgD-GC B cells. IgD antibodies from IgD+IgM- cells acquired reactivity to multiple oral, airborne and commensal antigens through a mutation-dependent pathway involving both innate and adaptive signals. Thus, IgD-ME B cells may form a ready-to-use pre-plasmacellular reservoir for steady-state IgD responses likely aimed at enhancing nasopharyngeal homeostasis. One Sentence SummaryTonsillar atypical memory B cells form a ready-to-use pre-plasmacellular repertoire for IgD responses to common aerodigestive antigens.