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¹ Department of Microbiology and Immunology, Dartmouth Medical School, Lebanon, NH 03756
² Department of Pediatric and Adolescent Medicine, Mayo Foundation, Rochester, MN 55905
³ Department of Immunology, Mayo Foundation, Rochester, MN 55905

Address correspondence to Randolph J. Noelle, Dept. of Microbiology and Immunology, Dartmouth Medical School, 1 Medical Center Dr., Lebanon, NH 03756. Phone: (603) 653-9908; Fax: (603) 653-9900; email: rjn{at}dartmouth.edu

Long-lived humoral immunity is manifested by the ability of bone marrow plasma cells (PCs) to survive for extended periods of time. Recent studies have underscored the importance of BLyS and APRIL as factors that can support the survival of B lineage lymphocytes. We show that BLyS can sustain PC survival in vitro, and this survival can be further enhanced by interleukin 6. Selective up-regulation of Mcl-1 in PCs by BLyS suggests that this -apoptotic gene product may play an important role in PC survival. Blockade of BLyS, via transmembrane activator and cyclophilin ligand interactor–immunoglobulin treatment, inhibited PC survival in vitro and in vivo. Heightened expression of B cell maturation antigen (BCMA), and lowered expression of transmembrane activator and cyclophilin ligand interactor and BAFF receptor in PCs relative to resting B cells suggests a vital role of BCMA in PC survival. Affirmation of the importance of BCMA in PC survival was provided by studies in BCMA^-/- mice in which the survival of long-lived bone marrow PCs was impaired compared with wild-type controls. These findings offer new insights into the molecular basis for the long-term survival of PCs.

Key Words: B lymphocyte subsets • antibody formation • cell differentiation • cell lineage • immunophenotyping

The online version of this article includes supplemental material.

The present address of W.J. Cook is GlycoFi, Inc., Lebanon, NH 03756.

Abbreviations used in this paper: ASC, antibody-secreting cell; BCMA, B cell maturation antigen; BSS, balanced salt solution; GC, germinal center; MZ, marginal zone; PC, plasma cell; TACI, transmembrane activator and cyclophilin ligand interactor; TD, T cell–dependent; TI, T cell–independent.

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