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Regulated Expression of BAFF-Binding Receptors during Human B Cell Differentiation¹

Department of Immunology, Mayo Clinic College of Medicine, Mayo Graduate School, Rochester MN 55905

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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by National Institutes of Health Grants CA105258 and CA062242 (to D.F.J.) and a predoctoral fellowship AI061838 (to J.R.D.).

² Address correspondence and reprint requests to Dr. Diane F. Jelinek, 200 First Street Southwest, Rochester, MN 55905. E-mail address: Jelinek.Diane{at}mayo.edu

³ Abbreviations used in this paper: BAFF, B cell-activating factor belonging to the TNF family; BAFF-R, BAFF receptor; ISC, Ig-secreting cell; TACI, transmembrane activator and calcium-modulating cyclophilin ligand interactor; BCMA, B cell maturation Ag; CSR, class switch recombination; PC, plasma cell; BM, bone marrow; MB, memory B cell; GC, germinal center; BBR, BAFF-binding receptor; PB, peripheral blood; CD40L, CD40 ligand; AID, activation-induced cytidine deaminase; MM, multiple myeloma.

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