Regulated expression of BAFF-binding receptors during human B cell differentiation.
BAFF plays a central role in B-lineage cell biology; however, the regulation of BAFF-binding receptor (BBR) expression during B cell activation and differentiation is not completely understood. In this study, we provide a comprehensive ex vivo analysis of BBRs in human B-lineage cells at various stages of maturation, as well as describe the events that drive and regulate receptor expression. Our data reveal that B-lineage cells ranging from naive to plasma cells (PCs), excluding bone marrow PCs, express BAFF-R uniformly. In contrast, only tonsillar memory B cells (MB) and PCs, from both tonsil and bone marrow tissues, express BCMA. Furthermore, we show that TACI is expressed by MB cells and PCs, as well as a subpopulation of activated CD27(neg) B cells. In this regard, we demonstrate that TACI is inducible early upon B cell activation and this is independent of B cell turnover. In addition, we found that TACI expression requires activation of the ERK1/2 pathway, since its expression was blocked by ERK1/2-specific inhibitors. Expression of BAFF-R and B cell maturation Ag (BCMA) is also highly regulated and we demonstrate that BCMA expression is only acquired in MB cells and in a manner accompanied by loss of BAFF-R expression. This inverse expression coincides with MB cell differentiation into Ig-secreting cells (ISC), since blocking differentiation inhibited both induction of BCMA expression and loss of BAFF-R. Collectively, our data suggest that the BBR profile may serve as a footprint of the activation history and stage of differentiation of normal human B cells.
Darce
Jaime R
JR
Department of Immunology, Mayo Clinic College of Medicine, Mayo Graduate School, Rochester MN 55905, USA.
Arendt
Bonnie K
BK
Wu
Xiaosheng
X
Jelinek
Diane F
DF
D053265:B-Cell Activation Factor Receptor / Q000096:biosynthesis*; D053301:B-Cell Maturation Antigen / Q000096:biosynthesis; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002070:Butadienes / Q000494:pharmacology; D002454:Cell Differentiation / Q000276:immunology; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000276:immunology; D048052:Mitogen-Activated Protein Kinase 3 / Q000276:immunology; D009570:Nitriles / Q000494:pharmacology; D015398:Signal Transduction / Q000276:immunology; D053303:Transmembrane Activator and CAML Interactor Protein / Q000037:antagonists & inhibitors / Q000096:biosynthesis
D053265:B-Cell Activation Factor Receptor; D053301:B-Cell Maturation Antigen; D002070:Butadienes; D005419:Flavonoids; D009570:Nitriles; C108467:TNFRSF13B protein, human; C435926:TNFRSF13C protein, human; D053303:Transmembrane Activator and CAML Interactor Protein; C113580:U 0126; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one