Defining the immunological phenotype of Fc receptor-like B (FCRLB) deficient mice: Confounding role of the inhibitory FcγRIIb.
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 FcγRIIb is located nearby Fcrlb. Although Fcrlb-gene targeting had no effect on the function or basal expression of FcγRIIb, 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 FcγRIIb 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.
Masuda
Keiji
K
Research Center for Allergy and Immunology, RIKEN Yokohama Institute, Japan.
Mori
Hiromi
H
Ohara
Osamu
O
Nakayama
Manabu
M
Wang
Ji-Yang
JY
Burrows
Peter D
PD
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology / Q000494:pharmacology; D000974:Antibodies, Antinuclear / Q000097:blood / Q000276:immunology; D000917:Antibody Formation / Q000235:genetics / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D002452:Cell Count; D049109:Cell Proliferation / Q000187:drug effects; D015870:Gene Expression / Q000235:genetics; D007140:Immunoglobulin Fab Fragments / Q000276:immunology / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009596:Nitrophenols / Q000276:immunology; D010648:Phenylacetates / Q000276:immunology; D011110:Polymorphism, Genetic / Q000235:genetics / Q000276:immunology; D011401:Promoter Regions, Genetic / Q000235:genetics; D011961:Receptors, Fc / Q000172:deficiency* / Q000235:genetics; D017452:Receptors, IgG / Q000235:genetics / Q000378:metabolism*; D014611:Vaccination
D000888:Antibodies, Anti-Idiotypic; D000974:Antibodies, Antinuclear; C499172:Fcgr2b protein, mouse; C504210:Fcrlm2 protein, mouse; D007140:Immunoglobulin Fab Fragments; D008070:Lipopolysaccharides; D009596:Nitrophenols; D010648:Phenylacetates; D011961:Receptors, Fc; D017452:Receptors, IgG; C044203:anti-IgM; C026242:4-hydroxy-5-nitrophenyl acetic acid