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Cutting Edge: The Dependence of Plasma Cells and Independence of Memory B Cells on BAFF and APRIL¹

Micah J. Benson^*, Stacey R. Dillon, Emanuela Castigli, Raif S. Geha, Shengli Xu, Kong-Peng Lam and Randolph J. Noelle^2,*

^* Department of Microbiology and Immunology, Dartmouth Medical School and The Norris Cotton Cancer Center, Lebanon, NH 03756; Department of Autoimmunity and Inflammation, ZymoGenetics, Inc., Seattle, WA 98102; Children’s Hospital Boston, Division of Immunology, Boston, MA 02115; and Singapore Immunology Network Laboratory of Immune Regulation, Agency for Science, Technology, and Research, Singapore

Memory B (B_MEM) cells and long-lived bone marrow plasma cells (BM-PCs) persist within local environmental survival niches that afford cellular longevity. However, the factors supporting B_MEM cell survival within the secondary lymphoid organs and allowing BM-PC persistence in the bone marrow remain poorly characterized. We report herein that long-lived B_MEM cell survival and function are completely independent of BAFF (B cell-activating factor of the TNF family) or APRIL (a proliferation-inducing ligand). Thus, B_MEM cells represent the only mature B2 lineage subset whose survival is independent of these ligands. We have previously shown that the TNFR family member receptor BCMA (B cell maturation Ag) is a critical survival receptor for BM-PC survival in vivo. We identify in this study the ligands critical for BM-PC survival and show that either BAFF or APRIL supports the survival of BM-PCs in vivo. These data define the BAFF/APRIL-dependent and -independent components of long-lived humoral immunity.

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 (NIH) Grants A1026296 and A108896 to R.J.N. and a NIH predoctoral training grant to M.J.B.

² Address correspondence and reprint requests to Dr. Randolph J. Noelle, Norris Cotton Cancer Center, One Medical Center Drive, Rubin Building, Level 7, HB 7937, Lebanon, NH 03756. E-mail address: Randolph.Noelle{at}Dartmouth.edu

³ Abbreviations used in this paper: B_MEM cell, memory B cell; APRIL, a proliferation inducing ligand; BAFF, B cell activating factor of the TNF family; BAFF-R, BAFF receptor; BCMA, B cell maturation Ag; BM, bone marrow; BM-PC, bone marrow plasma cell; GC, germinal center; het, heterozygous; KLH, keyhole limpet hemocyanin; mFc4, mutated Fc 4 region; NF, naive follicular (B cell); NP, (4-hydroxy-3-nitrophenyl)acetyl; PC, plasma cell; Spl-PC, splenic plasma cell; TACI, transmembrane activator and calcium modulator ligand interactor.