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.