Antibodies Encoded by FCRL4-Bearing Memory B Cells Preferentially Recognize Commensal Microbial Antigens

FCRL4, a low-affinity IgA Ab receptor with strong immunoregulatory potential, is an identifying feature of a tissue-based population of memory B cells (Bmem). We used two independent approaches to perform a comparative analysis of the Ag receptor repertoires of FCRL4⁺ and FCRL4^- Bmem in human tonsils. We determined that FCRL4⁺ Bmem displayed lower levels of somatic mutations in their Ag receptors compared with FCRL4^- Bmem but had similar frequencies of variable gene family usage. Importantly, Abs with reactivity to commensal microbiota were enriched in FCRL4⁺ cells, a phenotype not due to polyreactive binding characteristics. Our study links expression of the immunoregulatory FCRL4 molecule with increased recognition of commensal microbial Ags.