Defining the immunological phenotype of Fc receptor-like B (FCRLB) deficient mice: Confounding role of the inhibitory Fc gamma RIIb

Fc receptor-like A (FCRLA) and FCRLB have homology to the transmembrane FCRL family members (FCRL 1-6) and to the conventional receptors for the Fc portion of immunoglobulin, but uniquely are cytosolic proteins expressed in B cells. Here we describe the phenotype of Fcrlb-gene targeted mice. B cell development and in vitro responses are normal: however, antibody responses to a T-dependent antigen are elevated. The gene encoding the inhibitory Fc gamma RIIb is located nearby Fcrlb. Although Fcrlb-gene targeting had no effect on the function or basal expression of Fc gamma RIIb, its expression was reduced following activation. This abnormal regulation was due to co-inheritance of Fcgr2b and the mutant Fcrlb allele from the 129 ES cells. A promoter polymorphism in the 129/Sv Fcgr2b allele results in diminished upregulation of Fc gamma RIIb following B cell activation. Thus, we speculate that the enhanced antibody response seen in the FCRLB-deficient mice may be due to the Fcgr2b promoter. (C) 2010 Elsevier Inc. All rights reserved.