Fc receptor-like A associates with intracellular IgG and IgM but is dispensable for antigen-specific immune responses.

FcR-like (FcRL) proteins comprise a family of lymphocyte receptors with homology to FcgammaRI. Among these receptors, FcRLA is uniquely interesting due to its intracellular localization, unusual structural features, and high expression within human germinal center and marginal zone B cells. Our analysis of human cell lines has confirmed that this receptor is not secreted but is maintained as an intracellular protein in B cells where it interacts with Igs, consistent with a possible role in Ab assembly. By generating FcRLA-specific antisera as well as knockout mice, we were able to unequivocally demonstrate that FcRLA protein is expressed exclusively in all mouse B cells. We also found that FcRLA is not required for the generation of Ag-specific humoral immune responses to T-dependent or T-independent Ags. However, given its highly conserved structure and universal expression within B cells, it is probable that FcRLA functions similarly in humans and mice. Cumulatively, our data suggest that FcRLA plays a role in Ig assembly that can be compensated for by other proteins.