Regulated expression of BAFF-binding receptors during human B cell differentiation

Jaime R. Darce, Bonnie K. Arendt, Xiaosheng Wu, Diane F Jelinek

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161 Citations (Scopus)

Abstract

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 CD27neg 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.

Original languageEnglish (US)
Pages (from-to)7276-7286
Number of pages11
JournalJournal of Immunology
Volume179
Issue number11
StatePublished - Dec 1 2007

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B-Cell Activation Factor Receptor
Cell Differentiation
B-Lymphocytes
Plasma Cells
MAP Kinase Signaling System
Palatine Tonsil

ASJC Scopus subject areas

  • Immunology

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Regulated expression of BAFF-binding receptors during human B cell differentiation. / Darce, Jaime R.; Arendt, Bonnie K.; Wu, Xiaosheng; Jelinek, Diane F.

In: Journal of Immunology, Vol. 179, No. 11, 01.12.2007, p. 7276-7286.

Research output: Contribution to journalArticle

Darce, Jaime R. ; Arendt, Bonnie K. ; Wu, Xiaosheng ; Jelinek, Diane F. / Regulated expression of BAFF-binding receptors during human B cell differentiation. In: Journal of Immunology. 2007 ; Vol. 179, No. 11. pp. 7276-7286.
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